Clinical Faculty Orientation Practices in the United States: A Descriptive Study.

BACKGROUND: Due to the nursing faculty shortage, expert clinical nurses are working as novice clinical instructors (CIs). Orientation is needed to prepare these nurses to teach; however, lack of evidence-based guidelines for orientation programs can lead to variability among institutions. PURPOSE: The purpose of this study was to describe clinical nursing faculty orientation practices in the United States. METHODS: A descriptive convergent mixed methods design was used. RESULTS: One hundred thirteen CIs participated. Of these, 70.8% were not provided with a formal orientation to their role. Duration, modality, and content varied widely among orientations. Four themes were derived from the qualitative data: Administrative Requirements, Transition to Clinical Educator, Mentorship, and Resilience. CONCLUSIONS: Clinical faculty orientation practices vary widely in the United States. Evidence-based guidelines are needed to streamline orientations to provide CIs with the requisite knowledge and skills to support clinical students.

Oral nicotine product marketing expenditures in the USA from 2016 to 2023: trends over time by brand and targeted media outlets.

BACKGROUND: Oral nicotine products (ONPs) are increasing in sales, availability and flavours. In April 2022, the US Food and Drug Administration (FDA) obtained regulatory authority over non-tobacco nicotine products, which include many ONPs. Advertising practices for ONPs need monitoring to understand marketing strategies and inform FDA marketing authorisation decisions. METHODS: ONP advertisement (ad) expenditure data (January 2016-June 2023) were purchased (print, TV, radio, online video, online display and mobile; N=125 236) and adjusted to 2023 dollars. Descriptive statistics examined expenditures by ONP brand and media outlet over time. RESULTS: Velo spent the most on ONP advertising (89.8%), followed by Zyn (5.7%) and Black Buffalo (1.2%). Velo encompassed the majority of TV (98.1%), radio (99.9%) and mobile ad spend (87.3%); Zyn was the leader for online display (46.2%) and online video (71.1%); and Black Buffalo accounted for 100% of print ads. In 2023, (January-June), Zyn accounted for 88.0% of ad expenditures and Velo spent $0, though the total amount spent by Zyn was far less than Velo in prior years. TV ads (98.1% Velo) aired primarily on prime time/late night or 09:00-17:00 on weekends. Radio ads (99.9% Velo) aired primarily from 06:00 to 10:00, 12:00 to 14:00 and 15:00 to 19:00 on weekdays. Overall, expenditures focused on reaching a national audience, though print ads indicated potential male-targeted marketing. CONCLUSIONS: Following FDA's regulatory authority over non-tobacco nicotine products, ad expenditures for Velo dropped to $0. Ongoing surveillance of ONP ad trends can inform FDA marketing authorisation decisions by revealing brand-specific marketing strategies that may be targeted toward populations at increased risk of tobacco use.

Achieving Public Health Impact: Health Communication Research to Inform Tobacco Regulatory Science.

Health communication research applies communication science to develop generalizable knowledge capable of improving the health and well-being of individuals and communities. But to what extent does the knowledge generated by the health communication field actually achieve public health impact? To answer this question, we discuss the application of health communication science and research within a tobacco regulatory science framework. We describe three areas in which health communication research funded by the Food and Drug Administration (FDA) Center for Tobacco Products (CTP) contributed to 1) youth tobacco prevention campaigns, 2) cigarette health warnings, and 3) regulation of labeling, advertising, and marketing claims. These examples demonstrate how communication regulatory science achieves public health impact in the real world by informing national policies, regulatory actions, and public health practice.

Ionic strength alters crosslinker-driven self-organization of microtubules.

The microtubule cytoskeleton is a major structural element inside cells that directs self-organization using microtubule-associated proteins and motors. It has been shown that finite-sized, spindle-like microtubule organizations, called "tactoids," can form in vitro spontaneously from mixtures of tubulin and the antiparallel crosslinker, MAP65, from the MAP65/PRC1/Ase family. Here, we probe the ability of MAP65 to form tactoids as a function of the ionic strength of the buffer to attempt to break the electrostatic interactions binding MAP65 to microtubules and inter-MAP65 binding. We observe that, with increasing monovalent salts, the organizations change from finite tactoids to unbounded length bundles, yet the MAP65 binding and crosslinking appear to stay intact. We further explore the effects of ionic strength on the dissociation constant of MAP65 using both microtubule pelleting and single-molecule binding assays. We find that salt can reduce the binding, yet salt never negates it. Instead, we believe that the salt is affecting the ability of the MAP65 to form phase-separated droplets, which cause the nucleation and growth of tactoids, as recently demonstrated.

Prevalence and correlates of flavored novel oral nicotine product use among a national sample of youth.

BACKGROUND: Flavored novel oral nicotine products (ONP), such as pouches, gum, lozenges, tablets, and gummies, have recently entered the US market but have not been authorized for smoking cessation. This study assessed the prevalence and correlates of ONPs in a national sample of youth who smoked little filtered cigars or cigarillos (LCCs) or were susceptible to LCCs. METHODS: We conducted a national online survey from September-October 2022, as part of a study to develop cigar warnings among youth. Those aged 15-20 years old who reported using (ever or current) or susceptibility to little filtered cigars or cigarillos (LCCs) were eligible. Descriptive statistics and chi-square analyses assessed the prevalence of flavored ONP use and associations with other past 30-day tobacco product use and participant characteristics. RESULTS: Approximately one-fifth (17.1 %) of the sample (n = 680) reported past month flavored ONP use. Any past month tobacco use was correlated with past month flavored ONP use (ps < 0.001), increasing from 17.1 % in the overall sample to 26.8 % among those reporting e-cigarette use, 41.4 % (LCCs), 47.8 % (waterpipe tobacco), 61.8 % (large cigars), and 69.1 % (smokeless tobacco). The number of products used in the past month was significantly associated with higher odds of ONPs in the past month in a multivariable logistic regression model (aOR2.26; 95 % CI: 1.92, 2.65). DISCUSSION: Almost one-fifth of participants who use or are susceptible to cigar use in our national sample of youth use ONPs. Dual/poly use of other tobacco products and ONPs among youth suggests that many of these youth may be addicted to nicotine. Additional surveillance and regulation of ONPs that exhibit enticing characteristics, such as flavors, kid-friendly formulations, and targeted marketing/branding may be needed.

Compliance With US Federal Regulations on Waterpipe Tobacco Warnings on Packaging.

This cohort study reports the rate and degree of compliance with the Food and Drug Administration­mandated warning labels among waterpipe tobacco brands and products.

Differences in Normative Beliefs and Tobacco Product Use by Age Among Adults Who Smoke: Cross-Sectional Analysis of a Nationally Representative Sample.

BACKGROUND: The prevalence of combusted cigarette (CC) smoking among older adults is stagnant, with 0 declines attributable to e-cigarette (EC) use. Given that normative beliefs are associated with quitting and switching to ECs, we assessed cross-sectional associations between age, CC, and EC descriptive and injunctive norms and potential interactions with tobacco use behavior. METHODS: Data are from people with current, established (≥100 lifetime CCs) CC use (n = 8072) at Wave 5 (2018-2019) of the adult Population Assessment of Tobacco and Health Study. We used adjusted multivariable logistic regressions to model social norms as a function of age (18-24, 25-34, 35-44, 45-54, 55-64, ≥65 years). We also dichotomized age (≥55 vs 18-54) to investigate interactions between age and social norms on past 12-month CC quit attempts and past-month EC use. RESULTS: Older age was positively associated with pro- and anti-CC norms and anti-EC norms. Significant interactive effects revealed that being advised to quit smoking by a healthcare provider was more strongly associated with CC quit attempts among adults ≥55 years (adjusted odds ratio [aOR] [95% CI]: 2.12 [1.66, 2.71]) than adults <55 years (aOR: 1.63 [1.34, 2.00]). Reporting people close to you use ECs was also more strongly associated with EC use among adults ≥55 years (aOR: 4.37 [3.35, 5.69]) than among adults <55 years (aOR: 3.43 [2.89, 4.08]). CONCLUSIONS: This study identified modifiable risk factors for tobacco use that may be particularly beneficial for older adults. Behavioral and communication interventions that target normative beliefs may maximize smoking cessation, or harm reduction when cessation is not possible.

Impact of Vaccination and Nonpharmaceutical Interventions With Possible COVID-19 Viral Evolutions Using an Agent-Based Simulation.

Introduction: The COVID-19 pandemic continues with highly contagious variants and waning immunity. As the virus keeps evolving to be more infectious and immune evasive, some question whether the COVID-19 pandemic can be managed through sustainable public health measures. Methods: We developed an agent-based simulation to explore the impact of COVID-19 mutations, periodic vaccinations, and nonpharmaceutical interventions on reducing COVID-19 deaths. The model is calibrated to the greater Seattle area by observing local epidemic data. We perform scenario analyses on viral mutations that change infectiousness, disease severity, and immune evasiveness from previous infections and vaccination every 6 months. The simulation is run until the end of year 2023. Results: Variants with increased infectivity or increased immune evasion dominate previous strains. With enhanced immune protection from a pancoronavirus vaccine, the most optimistic periodic vaccination rate reduces average total deaths by 44.6% compared with the most pessimistic periodic vaccination rate. A strict threshold nonpharmaceutical intervention policy reduces average total deaths by 71.3% compared with an open society, whereas a moderate nonpharmaceutical intervention policy results in a 33.6% reduction. Conclusions: Our findings highlight the potential benefits of pancoronavirus vaccines that offer enhanced and longer-lasting immunity. We emphasize the crucial role of nonpharmaceutical interventions in reducing COVID-19 deaths regardless of virus mutation scenarios. Owing to highly immune evasive and contagious SARS-CoV-2 variants, most scenarios in this study fail to reduce the mortality of COVID-19 to the level of influenza and pneumonia. However, our findings indicate that periodic vaccinations and a threshold nonpharmaceutical intervention policy may succeed in achieving this goal. This indicates the need for caution and vigilance in managing a continuing COVID-19 epidemic.

Non-specific cargo-filament interactions slow down motor-driven transport.

Active, motor-based cargo transport is important for many cellular functions and cellular development. However, the cell interior is complex and crowded and could have many weak, non-specific interactions with the cargo being transported. To understand how cargo-environment interactions will affect single motor cargo transport and multi-motor cargo transport, we use an artificial quantum dot cargo bound with few (~ 1) to many (~ 5-10) motors allowed to move in a dense microtubule network. We find that kinesin-driven quantum dot cargo is slower than single kinesin-1 motors. Excitingly, there is some recovery of the speed when multiple motors are attached to the cargo. To determine the possible mechanisms of both the slow down and recovery of speed, we have developed a computational model that explicitly incorporates multi-motor cargos interacting non-specifically with nearby microtubules, including, and predominantly with the microtubule on which the cargo is being transported. Our model has recovered the experimentally measured average cargo speed distribution for cargo-motor configurations with few and many motors, implying that numerous, weak, non-specific interactions can slow down cargo transport and multiple motors can reduce these interactions thereby increasing velocity.

Effects of cytoskeletal network mesh size on cargo transport.

Intracellular transport of cargoes in the cell is essential for the organization and functioning cells, especially those that are large and elongated. The cytoskeletal networks inside large cells can be highly complex, and this cytoskeletal organization can have impacts on the distance and trajectories of travel. Here, we experimentally created microtubule networks with varying mesh sizes and examined the ability of kinesin-driven quantum dot cargoes to traverse the network. Using the experimental data, we deduced parameters for cargo detachment at intersections and away from intersections, allowing us to create an analytical theory for the run length as a function of mesh size. We also used these parameters to perform simulations of cargoes along paths extracted from the experimental networks. We find excellent agreement between the trends in run length, displacement, and trajectory persistence length comparing the experimental and simulated trajectories.

The Development and Testing of a Point-of-Sale E-Cigarette Health Communication Campaign.

Adolescents and young adults continue to use e-cigarettes, and communication campaigns are needed to decrease use among these populations. We developed and tested a point-of-sale communication campaign focused on e-cigarette chemical exposure. We developed messages based on formative research and tested them (versus text-only messages) in a nationally-representative online survey among adolescents and young adults (16-25) (Phase 1). Based on survey findings, we selected a message focused on nicotine and brain development for the point-of-sale trial (Phase 2). We then conducted a cluster-randomized trial at six gas stations with convenience stores, randomly assigned to the intervention (messages displayed) or no message control condition. We conducted intercept surveys with repeated cross-sectional samples of 50 participants (ages 16-25) per store, at baseline and a four-week follow-up. Phase 1 included 1,636 participants in the online study. Intervention messages were rated as more attention grabbing than plain text messages (p < .05), though were rated similarly on other outcomes. Exposure to intervention messages resulted in larger changes from pre- to posttest for beliefs about addiction and relative harms versus cigarettes (p < .05). Phase 2 included 586 participants in the point-of-sale study. Real-world campaign exposure was low (31.8%), and no differences were found between conditions. E-cigarette prevention messages focused on nicotine's impact on brain development show promise. However, garnering attention for communication campaigns in saturated point-of-sale environments, often dominated by tobacco advertising, is challenging. Future efforts should utilize additional communication channels to directly target adolescents and young adults.

Perceived effectiveness of cigar warnings in discouraging blunt use.

INTRODUCTION: Many people remove the tobacco leaf from cigars and replace it with cannabis (i.e., blunts), but few studies have examined whether messages about the risks of cigars, like warnings on cigar packages, can affect blunt use. METHODS: Participants were 438 US adults who reported past 30-day cigar use and ever blunt use, recruited from a probability-based national panel to take an online survey. In a 2x2 experiment with a between-subjects design, we manipulated two cigar warning characteristics: 1) warning type: text-only vs. pictorial (i.e., text + image) and 2) warning size: 30% (smaller) vs. 50% (larger) of the product package. Participants then viewed 6 different warnings on a fictious cigarillo package, within their randomly assigned condition. After evaluating all stimuli, participants were asked the extent to which the warnings discouraged them from wanting to use cigars to smoke cannabis (i.e., blunt perceived warning effectiveness). Response options ranged from "not at all" (1) to "a great deal" (5). RESULTS: We observed no main effects of warning type or size on blunt perceived warning effectiveness. However, a significant interaction existed between the two experimental manipulations (p=0.009). Whereas adding images made no difference to blunt perceived warning effectiveness when warnings were smaller (simple effect: -0.22, p=0.28), images mattered for larger warnings. Specifically, adding images increased blunt perceived warning effectiveness when warnings were 50% of the product package (simple effect: 0.52, p=0.008). CONCLUSIONS: This experiment provides preliminary evidence that larger pictorial cigar warnings may discourage blunt use relative to larger but text-only warnings. IMPLICATIONS: Blunts, which are hollowed out cigars with tobacco leaf wrappers that are filled with cannabis leaf, are one of the most common ways in which tobacco and cannabis are used simultaneously, yet few studies have examined whether messages about the risks of cigars can affect blunt use. We conducted an online experiment concerning the perceived effectiveness of cigar warnings among people who use blunts recruited from a probability-based panel. Results provide novel, preliminary evidence that larger pictorial cigar warnings may discourage blunt use, relative to larger but text-only warnings. More research evaluating cigar warnings on blunt use is needed.

Preventing tuberculosis with community-based care in an HIV-endemic setting: a modeling analysis.

Introduction: Antiretroviral therapy (ART) and TB preventive treatment (TPT) both prevent tuberculosis (TB) disease and deaths among people living with HIV. Differentiated care models, including community-based care, can increase uptake of ART and TPT to prevent TB in settings with a high burden of HIV-associated TB, particularly among men. Methods: We developed a gender-stratified dynamic model of TB and HIV transmission and disease progression among 100,000 adults ages 15-59 in KwaZulu-Natal, South Africa. We drew model parameters from a community-based ART initiation and resupply trial in sub-Saharan Africa (Delivery Optimization for Antiretroviral Therapy, DO ART) and other scientific literature. We simulated the impacts of community-based ART and TPT care programs during 2018-2027, assuming that community-based ART and TPT care were scaled up to similar levels as in the DO ART trial (i.e., ART coverage increasing from 49% to 82% among men and from 69% to 83% among women) and sustained for ten years. We projected the number of TB cases, deaths, and disability-adjusted life years (DALYs) averted relative to standard, clinic-based care. We calculated program costs and incremental cost-effectiveness ratios from the provider perspective. Results: If community-based ART care could be implemented with similar effectiveness to the DO ART trial, increased ART coverage could reduce TB incidence by 27.0% (range 21.3% - 34.1%) and TB mortality by 36.0% (range 26.9% - 43.8%) after ten years. Increasing both ART and TPT uptake through community-based ART with TPT care could reduce TB incidence by 29.7% (range 23.9% - 36.0%) and TB mortality by 36.0% (range 26.9% - 43.8%). Community-based ART with TPT care reduced gender disparities in TB mortality rates by reducing TB mortality among men by a projected 39.8% (range 32.2% - 46.3%) and by 30.9% (range 25.3% - 36.5%) among women. Over ten years, the mean cost per DALY averted by community-based ART with TPT care was $846 USD (range $709 - $1,012). Conclusions: By substantially increasing coverage of ART and TPT, community-based care for people living with HIV could reduce TB incidence and mortality in settings with high burdens of HIV-associated TB and reduce TB gender disparities.

Kinesin and myosin motors compete to drive rich multiphase dynamics in programmable cytoskeletal composites.

The cellular cytoskeleton relies on diverse populations of motors, filaments, and binding proteins acting in concert to enable nonequilibrium processes ranging from mitosis to chemotaxis. The cytoskeleton's versatile reconfigurability, programmed by interactions between its constituents, makes it a foundational active matter platform. However, current active matter endeavors are limited largely to single force-generating components acting on a single substrate-far from the composite cytoskeleton in cells. Here, we engineer actin-microtubule (MT) composites, driven by kinesin and myosin motors and tuned by crosslinkers, to ballistically restructure and flow with speeds that span three orders of magnitude depending on the composite formulation and time relative to the onset of motor activity. Differential dynamic microscopy analyses reveal that kinesin and myosin compete to delay the onset of acceleration and suppress discrete restructuring events, while passive crosslinking of either actin or MTs has an opposite effect. Our minimal advection-diffusion model and spatial correlation analyses correlate these dynamics to structure, with motor antagonism suppressing reconfiguration and demixing, while crosslinking enhances clustering. Despite the rich formulation space and emergent formulation-dependent structures, the nonequilibrium dynamics across all composites and timescales can be organized into three classes-slow isotropic reorientation, fast directional flow, and multimode restructuring. Moreover, our mathematical model demonstrates that diverse structural motifs can arise simply from the interplay between motor-driven advection and frictional drag. These general features of our platform facilitate applicability to other active matter systems and shed light on diverse ways that cytoskeletal components can cooperate or compete to enable wide-ranging cellular processes.

Examining Cigar Pack Quantity Purchases by Cigar Type in the United States Between 2014 and 2017.

INTRODUCTION: We examined whether the proportion of cigar pack quantity usually purchased differed between 2014 and 2017 in the United States. METHODS: Data are from waves 1 and 4 of the Population Assessment of Tobacco and Health Study. The proportions of pack quantity purchases between waves for premium cigars, large cigars, cigarillos, and filtered cigars for 10-pack quantities (singles, 2-packs, 3-packs, 4-packs, 5-packs, 6-9-packs, 10-packs, 11--19-packs, 20-packs, ≥21 packs) were compared using Z-tests. We used multivariable linear regressions to examine factors associated with pack quantity. RESULTS: For premium cigars, most adults purchased singles, with 84.4% in 2014 and 88.7% in 2017. For large cigars, single purchases increased from 46.2% to 62.7% (p < .00001). Two-packs also increased, 3.1% to 10.2% (p < .00001), while 5-packs, 6-9 packs, 10-19-packs, and 20-packs decreased. For cigarillos, singles purchases increased from 51.9% to 57.5% (p = .0002). Two-packs also increased, 8.8% to 19.6% (p < .00001), while 3-packs, 4-packs, 5-packs, and 20-packs decreased. For filtered cigars, the most prevalent pack quantity shifted from 20-packs in 2014 (62.6%) to singles in 2017 (36.7%). Singles, 2-packs, 3-4-packs, and 5-packs increased while 11-19-packs, 20-packs, and ≥21 packs decreased. Days used were positively associated with pack quantity purchase for all cigar types in 2017, while the price was positively associated with premium cigar purchase. CONCLUSIONS: Between 2014 and 2017, the proportion of consumers who purchased singles remained at over 80% for premium cigars and increased for other cigars. Continued monitoring of use behaviors, including pack quantities by cigar type, is needed as the market and policy landscapes continue shifting. IMPLICATIONS: Single cigar purchases are prominent across cigar types. Five-packs and 20-packs were the second most common pack quantities across cigar types, with relatively low proportions for other pack quantities. These findings suggest adults consuming premium cigars consistently prefer singles, a pattern that was found across cigar types. However, when considering purchases made online, premium cigars are widely purchased in larger pack quantities. Age and race were associated with purchase for some cigar types at some years, days used were associated with the purchase quantity in 2017 for all cigar types, and price was positively associated across time periods for only premium cigar purchases. Thus, the factors associated with cigar pack quantity purchase remain unclear. As the cigar policy landscape shifts, continued monitoring of the purchase behaviors by cigar type will be important to better inform future cigar policies.

Improving Point-of-Sale Warnings for Single Cigars: Implications for Premium Cigars.

INTRODUCTION: For cigars sold individually without packaging, including many premium cigars, the US Food and Drug Administration (FDA) proposed that retailers display six warning statements on a sign at the point-of-sale (POS). AIMS AND METHODS: To examine the potential effectiveness of cigar warning signs, we conducted a between-subjects online experiment. Participants were 809 U.S. adults who reported using cigars (78% ever large cigar use, 49% past 30-day large cigar use) recruited from a probability-based panel. Participants viewed an image of a cigar store countertop with randomization to one of four conditions: (1) no warning sign, (2) a sign with six FDA proposed text-only warnings, (3) a sign with six novel text-only warnings, or (4) a sign with six novel text + image warnings. We used analysis of variance (ANOVA) models and post hoc Tukey tests to examine the results. RESULTS: The FDA-proposed text-only warning sign was perceived as less effective in discouraging participants from smoking cigars (M: 3.26, SD: 1.39; scale range: 1-5, where five indicates higher discouragement) compared with the novel text-only warning sign (M = 3.38, SD = 1.40) and the novel text + image warning sign (M = 3.65, SD = 1.34). The novel text + image warning sign increased discouragement from smoking cigars versus the FDA-proposed text-only warning sign (p = .02) and decreased the perceived satisfaction of smoking cigars versus no warning sign (p = .04). In a sensitivity analysis, the novel text + image warning sign decreased the perceived satisfaction of smoking cigars (p = .01), decreased cigar purchase intentions (p = .03), decreased the urge to smoke (p = .03), and increased discouragement from smoking cigars (p = .006) compared with all other study conditions. CONCLUSIONS: Results provide new evidence that policymakers, such as the FDA, could use when proposing POS warning signs for cigars. IMPLICATIONS: The US FDA proposed that retailers display a warning sign at the POS for cigars sold individually without packaging. We conducted an online experiment concerning the potential effectiveness of this regulatory policy with people who use cigars recruited from a probability-based panel. Results provide the first evidence that the FDA-proposed text-only warning sign was perceived as less effective than other types of warning signs and that adding images could potentially increase the effectiveness of warning signs. These findings are particularly relevant for premium cigars, which are often sold individually in brick-and-mortar retail settings.

Early Outcomes of SARS-CoV-2 Infection in a Multisite Prospective Cohort of Inpatient Veterans.

Background: Over 870 000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have occurred among Veterans Health Administration users, and 24 000 have resulted in death. We examined early outcomes of SARS-CoV-2 infection in hospitalized veterans. Methods: In an ongoing, prospective cohort study, we enrolled veterans age ≥18 tested for SARS-CoV-2 and hospitalized at 15 Department of Veterans Affairs medical centers between February 2021 and June 2022. We estimated adjusted odds ratios (aORs), adjusted incidence rate ratios (aIRRs), and adjusted hazard ratios (aHRs) for maximum illness severity within 30 days of study entry (defined using the 4-category VA Severity Index for coronavirus disease 2019 [COVID-19]), as well as length of hospitalization and rehospitalization within 60 days, in relationship with demographic characteristics, Charlson comorbidity index (CCI), COVID-19 vaccination, and calendar period of enrollment. Results: The 542 participants included 329 (61%) who completed a primary vaccine series (with or without booster; "vaccinated"), 292 (54%) enrolled as SARS-CoV-2-positive, and 503 (93%) men, with a mean age of 64.4 years. High CCI scores (≥5) occurred in 61 (44%) vaccinated and 29 (19%) unvaccinated SARS-CoV-2-positive participants. Severe illness or death occurred in 29 (21%; 6% died) vaccinated and 31 (20%; 2% died) unvaccinated SARS-CoV-2-positive participants. SARS-CoV-2-positive inpatients per unit increase in CCI had greater multivariable-adjusted odds of severe illness (aOR, 1.21; 95% CI, 1.01-1.45), more hospitalization days (aIRR, 1.06; 95% CI, 1.03-1.10), and rehospitalization (aHR, 1.07; 95% CI, 1.01-1.12). Conclusions: In a cohort of hospitalized US veterans with SARS-CoV-2 infection, those with a higher CCI had more severe COVID-19 illness, more hospital days, and rehospitalization, after adjusting for vaccination status, age, sex, and calendar period.

Interplay of self-organization of microtubule asters and crosslinking protein condensates.

The cytoskeleton is a major focus of physical studies to understand organization inside cells given its primary role in cell motility, cell division, and cell mechanics. Recently, protein condensation has been shown to be another major intracellular organizational strategy. Here, we report that the microtubule crosslinking proteins, MAP65-1 and PRC1, can form phase separated condensates at physiological salt and temperature without additional crowding agents in vitro. The size of the droplets depends on the concentration of protein. MAP65 condensates are liquid at first and can gelate over time. We show that these condensates can nucleate and grow microtubule bundles that form asters, regardless of the viscoelasticity of the condensate. The droplet size directly controls the number of projections in the microtubule asters, demonstrating that the MAP65 concentration can control the organization of microtubules. When gel-like droplets nucleate and grow asters from a shell of tubulin at the surface, the microtubules are able to re-fluidize the MAP65 condensate, returning the MAP65 molecules to solution. This work implies that there is an interplay between condensate formation from microtubule-associated proteins, microtubule organization, and condensate dissolution that could be important for the dynamics of intracellular organization.

Lateral and longitudinal compaction of PRC1 overlap zones drives stabilization of interzonal microtubules.

During anaphase, antiparallel-overlapping midzone microtubules elongate and form bundles, contributing to chromosome segregation and the location of contractile ring formation. Midzone microtubules are dynamic in early but not late anaphase; however, the kinetics and mechanisms of stabilization are incompletely understood. Using photoactivation of cells expressing PA-EGFP-α-tubulin we find that immediately after anaphase onset, a single highly dynamic population of midzone microtubules is present; as anaphase progresses, both dynamic and stable populations of midzone microtubules coexist. By mid-cytokinesis, only static, non-dynamic microtubules are detected. The velocity of microtubule sliding also decreases as anaphase progresses, becoming undetectable by late anaphase. Following depletion of PRC1, midzone microtubules remain highly dynamic in anaphase and fail to form static arrays in telophase despite furrowing. Cells depleted of Kif4a contain elongated PRC1 overlap zones and fail to form static arrays in telophase. Cells blocked in cytokinesis form short PRC1 overlap zones that do not coalesce laterally; these cells also fail to form static arrays in telophase. Together, our results demonstrate that dynamic turnover and sliding of midzone microtubules is gradually reduced during anaphase and that the final transition to a static array in telophase requires both lateral and longitudinal compaction of PRC1 containing overlap zones.