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Cardiac neural crest cells are essential for outflow tract remodeling in animals with divided systemic and pulmonary circulatory systems, but their contributions to cardiac development in animals with a single-loop circulatory system are less clear. Here we genetically labeled neural crest cells and examined their contribution to the developing zebrafish heart. We identified two populations of neural crest cells that contribute to distinct compartments of zebrafish cardiovascular system at different developmental stages. A stream of neural crest cells migrating through pharyngeal arches 1 and 2 integrates into the myocardium of the primitive heart tube between 24 and 30. h post fertilization and gives rise to cardiomyocytes. A second wave of neural crest cells migrating along aortic arch 6 envelops the endothelium of the ventral aorta and invades the bulbus arteriosus after three days of development. Interestingly, while inhibition of FGF signaling has no effect on the integration of neural crest cells to the primitive heart tube, it prevents these cells from contributing to the outflow tract, demonstrating disparate responses of neural crest cells to FGF signaling. Furthermore, neural crest ablation in zebrafish leads to multiple cardiac defects, including reduced heart rate, defective myocardial maturation and a failure to recruit progenitor cells from the second heart field. These findings add to our understanding of the contribution of neural crest cells to the developing heart and provide insights into the requirement for these cells in cardiac maturation.

Chromoblastomycosis, an implantation mycosis, is a neglected tropical disease that causes decreased quality of life, stigma, and disability. The global burden of disease is unknown and data on disease epidemiology and outcomes are severely limited by a lack of access to needed diagnostic tools and therapeutics. The World Health Organization outlined targets for chromoblastomycosis in the Road Map for Neglected Tropical Diseases 2021-2030, but little progress has been made in initiating and implementing an effective control program globally. This lack of guiding policy and progress led to the recent formation of a Global Chromoblastomycosis Working Group which has developed a global chromoblastomycosis strategy. We describe this strategy, which outlines specific steps needed to improve technical progress, strategy and service delivery, and enablers. Clinicians, researchers, public and government officials, patients, and policy makers can align their time, expertise, and resources to improve the lives of communities affected by chromoblastomycosis through this strategy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

For most Eukaryotic species the requirements of cilia formation dictate the structure of microtubule organizing centers (MTOCs). In this study we find that loss of cilia corresponds to loss of evolutionary stability for fungal MTOCs. We used iterative search algorithms to identify proteins homologous to those found in Saccharomyces cerevisiae, and Schizosaccharomyces pombe MTOCs, and calculated site-specific rates of change for those proteins that were broadly phylogenetically distributed. Our results indicate that both the protein composition of MTOCs as well as the sequence of MTOC proteins are poorly conserved throughout the fungal kingdom. To begin to reconcile this rapid evolutionary change with the rigid structure and essential function of the S. cerevisiae MTOC we further analyzed how structural interfaces among proteins influence the rates of change for specific residues within a protein. We find that a more stable protein may stabilize portions of an interacting partner where the two proteins are in contact. In summary, while the protein composition and sequences of the MTOC may be rapidly changing the proteins within the structure have a stabilizing effect on one another. Further exploration of fungal MTOCs will expand our understanding of how changes in the functional needs of a cell have affected physical structures, proteomes, and protein sequences throughout fungal evolution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Downregulation of intercellular communication through suppression of gap junctional conductance is necessary during wound healing. Connexin 43 (Cx43), a prominent gap junction protein in skin, is downregulated following wounding to restrict communication between keratinocytes. Previous studies found that PKCμ, a novel PKC isozyme, regulates efficient cutaneous wound healing. However, the molecular mechanism by which PKCμ regulates wound healing remains unknown. We have identified that PKCμ suppresses intercellular communication and enhances cell migration in an in vitro wound healing model by regulating Cx43 containing gap junctions. PKCμ can directly interact with and phosphorylate Cx43 at S368, which leads to Cx43 internalization and downregulation. Finally, utilizing phosphomimetic and non-phosphorylatable S368 substitutions and gap junction inhibitors, we confirmed that PKCμ regulates intercellular communication and in vitro wound healing by controlling Cx43-S368 phosphorylation. These results define PKCμ as a critical regulator of Cx43 phosphorylation to control cell migration and wound healing in keratinocytes., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: In 2021, a large petroleum leak contaminated a water source that supplied drinking water to military and civilians in Oahu, Hawaii., Methods: We conducted an Assessment of Chemical Exposures (ACE) survey and supplemented that information with complementary data sources: (1) poison center caller records; (2) emergency department visit data; and (3) a key informant questionnaire., Results: Among 2,289 survey participants, 86% reported ≥1 new or worsening symptom, 75% of which lasted ≥30 days, and 37% sought medical care. Most (n = 1,653, 72%) reported new mental health symptoms. Among equally observable symptoms across age groups, proportions of children ≤2 years experiencing vomiting, runny nose, skin rashes, and coughing (33, 46, 56, and 35%, respectively) were higher than other age groups. Poison center calls increased the first 2 weeks after the contamination, while emergency department visits increased in early December 2021. Key informant interviews revealed themes of lack of support, mental health symptoms, and long-term health impact concerns., Discussion: This event led to widespread exposure to petroleum products and negatively affected thousands of people. Follow-up health surveys or interventions should give special consideration to longer-term physical and mental health, especially children due to their unique sensitivity to environmental exposures.

Objective: Although vaccination reduces the risk of severe COVID-19, fatal COVID-19 cases after vaccination can occur. We examined the characteristics of decedents with COVID-19-related mortality to help inform discussions about vaccination, boosters, and mitigation strategies., Methods: We examined COVID-19-related deaths in Kentucky resulting from infections occurring from July 1 through August 13, 2021. We used records from case investigations, medical records, the Kentucky Health Information Exchange, and the Kentucky Immunization Registry to determine demographic information, vaccination status, and underlying health conditions, including calculation of the Charlson Comorbidity Index (CCI). We calculated mortality incidence rates by vaccination status by using data for unvaccinated and fully vaccinated populations in Kentucky as of July 1, 2021., Results: In total, 777 COVID-19-related deaths occurred in Kentucky during the study period; 592 (76.2%) occurred among unvaccinated people. Compared with unvaccinated decedents, fully vaccinated decedents were older (median age, 77 vs 65 years; P  < .001), had higher comorbidity levels (median CCI, 3 vs 1; P  < .001), and were more likely to have immunocompromised health status (26.4% vs 16.0%; P  = .003). Diabetes, hypertension, heart disease, and chronic lung disease were more common among vaccinated decedents than among unvaccinated decedents. Unvaccinated adults had a significantly higher risk of death than fully vaccinated adults (incidence rate ratio for age 20-49 years: 20.5 [95% CI, 6.5-64.8]; 50-64 years: 14.6 [95% CI, 9.4-22.7]; ≥65 years: 10.2 [95% CI, 8.3-12.4])., Conclusions: Immunocompromised health status, older age, and higher comorbidity were prevalent among fully vaccinated decedents, suggesting adults with these characteristics may benefit from additional protection strategies. Further understanding of the protection of additional and booster doses is needed.

On July 26, 2022, a pediatric nephrologist alerted The Gambia's Ministry of Health (MoH) to a cluster of cases of acute kidney injury (AKI) among young children at the country's sole teaching hospital, and on August 23, 2022, MoH requested assistance from CDC. CDC epidemiologists arrived in The Gambia, a West African country, on September 16 to assist MoH in characterizing the illness, describing the epidemiology, and identifying potential causal factors and their sources. Investigators reviewed medical records and interviewed caregivers to characterize patients' symptoms and identify exposures. The preliminary investigation suggested that various contaminated syrup-based children's medications contributed to the AKI outbreak. During the investigation, MoH recalled implicated medications from a single international manufacturer. Continued efforts to strengthen pharmaceutical quality control and event-based public health surveillance are needed to help prevent future medication-related outbreaks., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: COVID-19 vaccines are an effective tool to prevent illness due to SARS-CoV-2 infection. However, infection after vaccination still occurs. We evaluated all infections identified among recipients of either the Pfizer-BioNTech or Moderna COVID-19 vaccine in five U.S. states during January-March 2021., Methods: Using observational data reported to CDC, we compared the incidence of SARS-CoV-2 infection among vaccinated and unvaccinated persons, and the sex, age, and vaccine product received for individuals with vaccine breakthrough infections to those of the vaccinated population using Poisson regression models. We also compared the proportion of vaccine breakthrough cases due to a SARS-CoV-2 variant of concern to data reported to CDC's national genomic surveillance program., Results: The age-adjusted incidence of reported SARS-CoV-2 infection was 97% lower among vaccinated as compared to unvaccinated persons aged ≥ 16 years (68 vs 2252 cases per 100,000 people). Vaccinated adults aged ≥ 85 years were 1.6 times (95% CI 1.3-1.9) as likely to become infected with SARS-CoV-2 than vaccinated adults aged < 65 years. Pfizer-BioNTech COVID-19 vaccine recipients were 1.4 times (95% CI 1.3-1.6) as likely to experience infection compared to Moderna COVID-19 recipients. The proportion of infections among vaccinated persons caused by SARS-CoV-2 variants of concern was similar to the proportion of circulating viruses identified as variants of concern in the five states during the same time., Conclusions: Vaccinated persons had a substantially lower incidence of SARS-CoV-2 infection compared to unvaccinated persons. Adults aged ≥ 85 years and Pfizer-BioNTech vaccine recipients had a higher risk of infection following vaccination. We provide an analytic framework for ongoing evaluation of patterns associated with SARS-CoV-2 infection among vaccinated persons using observational surveillance and immunization data. Our findings reinforce the effectiveness of COVID-19 vaccines in preventing infection in real-world settings., (© 2022. The Author(s).)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Diana Felton reports grants from the Environmental Protection Agency for the Water Infrastructure Improvements for the Nation Act, multipurpose grants, grants from? the State Response Program, and travel support from the University of California at San Francisco (UCSF) Department of Occupational and Environmental Medicine (OEM) for travel to the 2022 UCSF OEM annual meeting and from the Association of State and Territorial Health Officials for attendance at the State Environmental Health Directors Annual Meeting (June 2022). No other potential conflicts of interest were disclosed.

This study investigated the utility of including teacher-reported callous-unemotional (CU) behaviors in the assessment of disruptive behaviors in school-based research. Participants included 138 first- and second-grade children (68% male; 76% eligible for free or reduced-price lunch; 61% Black, 9% Latinx, 23% White, and 7% multiracial) who completed assessments during the baseline assessment of an intervention study. Results indicated that teachers could distinguish CU from traditional indicators of disruptive behavior, including attention deficit hyperactivity disorder (ADHD) behaviors and conduct problems (CP). When considered alone, there was mixed evidence for the utility of CU behaviors. Although higher levels of CU behaviors explained unique variation in teacher-reported social competence and global impairment, CU behaviors did not explain unique variation in disciplinary infractions, classroom behavior, or academic functioning after accounting for ADHD and CP behaviors. A different pattern of results was evident when CU was considered in conjunction with ADHD and CP behaviors. Latent profile analyses identified three subgroups of participants (i.e., a nondisruptive group, an ADHD group, and a comorbid group, who exhibited elevated levels of ADHD, CP, and CU). Compared to the nondisruptive group, the ADHD group exhibited higher rates of off-task classroom behavior and worse academic functioning. The comorbid group exhibited moderate-to-large differences from both groups on teacher-reported and objective outcomes. The implications of these results are discussed with respect to the potential value of incorporating CU behaviors, which are becoming prominent in clinical psychology and psychiatry, into school-based research and for school psychology practice. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: As vaccine supply and access remain limited in many parts of the world, understanding the duration of protection from reinfection after natural infection is important., Methods: Distinct individuals testing positive and negative for SARS-CoV-2 between March 6, 2020, and August 31, 2020, in Kentucky, USA, were identified using the Kentucky National Electronic Disease Surveillance System. Individuals were followed for occurrence of a positive test for SARS-CoV-2 from 91 days after their initial test result through December 31, 2020. Protection from reinfection provided by a prior infection was calculated and additional analyses evaluated impact of age, sex, symptom status, long-term care facility connection, testing occurrence and frequency, and time from initial infection., Results: The protective effect from prior infection was 80.3% (95% CI, 78.2%-82.2%) for those aged 20-59 years and 67.4% (95% CI, 62.8%-71.4%) for those aged ≥60 years. At 30-day time periods through 270 days (with limited exceptions), protection was estimated to be >75% for those aged 20-59 years and >65% for those aged ≥60 years. Factors associated with repeat positive testing included a connection to a long-term care facility, duration of potential exposure, and absence of symptoms during initial infection., Conclusions: Natural infection provides substantial and persistent immunologic protection for a period of several months for most individuals, although subpopulations may be at greater risk of repeat positive testing and potential poor outcomes associated with reinfection. These subgroups include individuals aged ≥60 years, residents and staff of long-term care facilities, and those who have mild or asymptomatic illness with initial infection. Continued emphasis on vaccination and infection prevention and control strategies remains critically important in reducing the risk of reinfection and associated severe outcomes for these groups., (Published by Elsevier Ltd.)

Background: Racial disparities in the medical treatment of adults with arthritis are well-documented. Disparities with physical therapy treatment have yet to be thoroughly evaluated., Objective: To investigate the association of patient's race with physical therapy treatment recommendations for patients with arthritis., Design: Online survey., Methods: Physical therapists, physical therapist assistants, student physical therapists, and student physical therapist assistants within a Southern California county completed an online survey that presented a case vignette with a randomly assigned photograph of a White or Black woman. Recommendations for the plan of care included frequency of visits and number of exercises in the home exercise program (HEP), referrals to other healthcare professionals, and explicit ranking of how patient characteristics impacted the treatment planning were compared between respondents who viewed the Black or White patient., Results: Eighty-three participants completed the survey, and all participants reported that the patient was appropriate for physical therapy. Most participants (66.3%) reported that they would recommend a frequency of therapy of 2-3 times weekly. All participants recommended including a HEP. There were no statistically significant differences by patient race in recommendations for treatment frequency or referrals to other healthcare team members. HEP prescription was a median of four exercises, but participants who viewed the Black patient were more likely to recommend fewer exercises than those who viewed the White patient (p = 0.03). Explicitly, 96.1% of participants reported that race did not impact their treatment recommendations., Conclusions: In most aspects of treatment planning, the patient's race did not impact recommendations by physical therapy professionals. The lower exercise prescription assigned to the Black patient may represent a disparity that merits further attention., (© 2020. W. Montague Cobb-NMA Health Institute.)

Although laboratory evidence suggests that antibody responses following COVID-19 vaccination provide better neutralization of some circulating variants than does natural infection (1,2), few real-world epidemiologic studies exist to support the benefit of vaccination for previously infected persons. This report details the findings of a case-control evaluation of the association between vaccination and SARS-CoV-2 reinfection in Kentucky during May-June 2021 among persons previously infected with SARS-CoV-2 in 2020. Kentucky residents who were not vaccinated had 2.34 times the odds of reinfection compared with those who were fully vaccinated (odds ratio [OR] = 2.34; 95% confidence interval [CI] = 1.58-3.47). These findings suggest that among persons with previous SARS-CoV-2 infection, full vaccination provides additional protection against reinfection. To reduce their risk of infection, all eligible persons should be offered vaccination, even if they have been previously infected with SARS-CoV-2., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Although COVID-19 mRNA vaccines demonstrated high efficacy in clinical trials (1), they were not 100% efficacious. Thus, some infections postvaccination are expected. Limited data are available on effectiveness in skilled nursing facilities (SNFs) and against emerging variants. The Kentucky Department for Public Health (KDPH) and a local health department investigated a COVID-19 outbreak in a SNF that occurred after all residents and health care personnel (HCP) had been offered vaccination. Among 83 residents and 116 HCP, 75 (90.4%) and 61 (52.6%), respectively, received 2 vaccine doses. Twenty-six residents and 20 HCP received positive test results for SARS-CoV-2, the virus that causes COVID-19, including 18 residents and four HCP who had received their second vaccine dose >14 days before the outbreak began. An R.1 lineage variant was detected with whole genome sequencing (WGS). Although the R.1 variant has multiple spike protein mutations, vaccinated residents and HCP were 87% less likely to have symptomatic COVID-19 compared with those who were unvaccinated. Vaccination of SNF populations, including HCP, is critical to reduce the risk for SARS-CoV-2 introduction, transmission, and severe outcomes in SNFs. An ongoing focus on infection prevention and control practices is also essential., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Reinfection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is believed to be rare (1). Some level of immunity after SARS-CoV-2 infection is expected; however, the evidence regarding duration and level of protection is still emerging (2). The Kentucky Department for Public Health (KDPH) and a local health department conducted an investigation at a skilled nursing facility (SNF) that experienced a second COVID-19 outbreak in October 2020, 3 months after a first outbreak in July. Five residents received positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results during both outbreaks. During the first outbreak, three of the five patients were asymptomatic and two had mild symptoms that resolved before the second outbreak. Disease severity in the five residents during the second outbreak was worse than that during the first outbreak and included one death. Because test samples were not retained, phylogenetic strain comparison was not possible. However, interim period symptom resolution in the two symptomatic patients, at least four consecutive negative RT-PCR tests for all five patients before receiving a positive test result during the second outbreak, and the 3-month interval between the first and the second outbreaks, suggest the possibility that reinfection occurred. Maintaining physical distance, wearing face coverings or masks, and frequent hand hygiene are critical mitigation strategies necessary to prevent transmission of SARS-CoV-2 to SNF residents, a particularly vulnerable population at risk for poor COVID-19-associated outcomes.* Testing, containment strategies (isolation and quarantine), and vaccination of residents and health care personnel (HCP) are also essential components to protecting vulnerable residents. The findings of this study highlight the importance of maintaining public health mitigation and protection strategies that reduce transmission risk, even among persons with a history of COVID-19 infection., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Ploidy is the number of whole sets of chromosomes in a species. Ploidy is typically a stable cellular feature that is critical for survival. Polyploidization is a route recognized to increase gene dosage, improve fitness under stressful conditions and promote evolutionary diversity. However, the mechanism of regulation and maintenance of ploidy is not well characterized. Here, we examine the spontaneous diploidization associated with mutations in components of the Saccharomyces cerevisiae centrosome, known as the spindle pole body (SPB). Although SPB mutants are associated with defects in spindle formation, we show that two copies of the mutant in a haploid yeast favors diploidization in some cases, leading us to speculate that the increased gene dosage in diploids 'rescues' SPB duplication defects, allowing cells to successfully propagate with a stable diploid karyotype. This copy number-based rescue is linked to SPB scaling: certain SPB subcomplexes do not scale or only minimally scale with ploidy. We hypothesize that lesions in structures with incompatible allometries such as the centrosome may drive changes such as whole genome duplication, which have shaped the evolutionary landscape of many eukaryotes., Competing Interests: The authors declare no competing financial interests.

Importance: Although racial/ethnic differences in functional outcomes after total knee arthroplasty (TKA) exist, whether such differences are associated with differences in presurgical physical function (PF) has not been thoroughly investigated., Objective: To examine trajectories of PF by race/ethnicity before and after TKA among older women., Design, Setting, and Participants: This cohort study was conducted among the prospective Women's Health Initiative with linked Medicare claims data. A total of 10 325 community-dwelling women throughout the United States with Medicare fee-for-service underwent primary TKA between October 1, 1993, and December 31, 2014, and were followed up through March 31, 2017., Exposures: Race/ethnicity comparisons between Hispanic or Latina women, non-Hispanic black or African American women, and non-Hispanic white women (hereafter referred to as Hispanic, black, and white women, respectively)., Main Outcomes and Measures: Physical functioning scale scores and self-reported activity limitations with walking 1 block, walking several blocks, and climbing 1 flight of stairs were measured by the RAND 36-Item Health Survey during the decade before and after TKA, with a median of 9 PF measurements collected per participant over time., Results: In total, 9528 white women (mean [SD] age at surgery, 74.6 [5.5] years), 622 black women (mean [SD] age at surgery, 73.1 [5.3] years), and 175 Hispanic women (mean [SD] age at surgery, 73.1 [5.2] years) underwent TKA. During the decade prior to TKA, black women had lower PF scores than white women (mean difference, -5.8 [95% CI, -8.0 to -3.6]) and higher odds of experiencing difficulty walking a single block (5 years before TKA: odds ratio, 1.86 [95% CI, 1.57-2.21]), walking multiple blocks (odds ratio, 2.14 [95% CI, 1.83-2.50]), and climbing 1 flight of stairs (odds ratio, 1.81 [95% CI, 1.55-2.12]). After TKA, black women continued to have lower PF scores throughout the decade (mean difference 1 year after TKA, -7.8 [95% CI, -10.8 to -4.9]). After adjusting for preoperative PF scores, PF scores after TKA were attenuated (mean difference 1 year after TKA, -3.0 [95% CI, -5.3 to -0.7]), with no statistically significant differences in long-term follow-up. Hispanic women had similar PF scores to white women during the pre-TKA and post-TKA periods., Conclusions and Relevance: This study suggests that black women had significantly poorer PF than white women during the decades before and after TKA. Poorer PF after surgery was associated with poorer preoperative PF. Reducing disparities in post-TKA functional outcomes should target maintenance of function preoperatively in the early stages of arthritic disease and/or reduction of delays to receiving TKA once need arises.

Background: Racial disparities in functional outcomes after total knee arthroplasty (TKA) exist. Whether differences in rehabilitation utilization contribute to these disparities remains to be investigated., Methods: Among 8349 women enrolled in the prospective Women's Health Initiative cohort who underwent primary TKA between 2006 and 2013, rehabilitation utilization was determined through linked Medicare claims data. Postacute discharge destination (home, skilled nursing facility, and inpatient rehabilitation facility), facility length of stay, and number of home health physical therapy (HHPT) and outpatient physical therapy (OPPT) sessions were compared between racial groups., Results: Non-Hispanic black women had worse physical function (median score, 65 vs 70) and higher likelihood of disability (13.2% vs 6.9%) than non-Hispanic white women before surgery. After TKA, black women were more likely to be discharged postacutely to an institutional facility (64.3% vs 54.5%) than white women, were more likely to receive HHPT services (52.6% vs 47.8%), and received more HHPT and OPPT sessions. After stratification by postacute discharge setting, the likelihood of receipt of HHPT or OPPT services was similar between racial groups. No significant difference in receipt of HHPT or OPPT services was found after use of propensity score weighting to balance health and medical characteristics indicating severity of need for physical therapy services., Conclusion: Rehabilitation utilization was generally comparable between black and white women who received TKA when accounting for need. There was no evidence of underutilization of post-TKA rehabilitation services, and thus disparities in post-TKA functional outcomes do not appear to be a result of inequitable receipt of rehabilitation care., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate racial and ethnic disparities in utilization of total knee arthroplasty (TKA) in relation to demographic, health, and socioeconomic status variables., Design: Prospective study of 102,767 Women's Health Initiative postmenopausal women initially aged 50-79, examining utilization rates of primary TKA between non-Hispanic Black/African American, non-Hispanic White, and Hispanic/Latina women (hereafter referred to as Black, White, and Hispanic). A total of 8,942 Black, 3,405 Hispanic, and 90,420 White women with linked Medicare claims data were followed until time of TKA, death, or transition from fee-for-service coverage. Absolute disparities were determined using utilization rates by racial/ethnic group and relative disparities quantified using multivariable hazards models in adjusting for age, arthritis, joint pain, mobility disability, body mass index, number of comorbidities, income, education, neighborhood socioeconomic status (SES), and geographic region., Results: TKA utilization was higher among White women (10.7/1,000 person-years) compared to Black (8.5/1,000 person-years) and Hispanic women (7.6/1,000 person-years). Among women with health indicators for TKA including diagnosis of arthritis, moderate to severe joint pain, and mobility disability, Black and Hispanic women were significantly less likely to undergo TKA after adjusting for age [Black: HR (95% confidence interval) = 0.70 (0.63-0.79); Hispanic: HR = 0.58 (0.44-0.77)]. Adjustment for SES modestly attenuated the measured disparity, but significant differences remained [Black: HR = 0.75 (0.67-0.89); Hispanic: HR = 0.65 (0.47-0.89)]., Conclusions: Compared to White women, Black and Hispanic women were significantly less likely to undergo TKA after considering need and appropriateness for TKA and SES. Further investigation into personal-level and provider-level factors that may explain these disparities is warranted., (Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objectives: Latina mothers in emerging immigrant communities experience heightened risk for depressive symptoms because of the convergence of multiple risk factors rooted in economic, cultural, and familial experiences. Previous research with Latina/o adolescents has found that discrimination, and not acculturative stress, predicts depressive symptoms; however, no research to our knowledge has examined the relative impact of both discrimination and acculturative stress in Latina mothers., Method: The present study expands this literature by examining how both universal (i.e., economic hardship and parent-child conflict) and cultural stressors (i.e., discrimination and acculturative-based family conflict) predict maternal depressive symptoms in a sample of 169 Latina mothers in an emerging immigrant context., Results: Results found that the presence of universal stressors for Latina mothers does indeed significantly predict depressive symptoms, and that uniquely, 1 type of cultural stressor (i.e., acculturative-based family conflict) predicts depressive symptoms above and beyond the universal stressors., Conclusions: These findings indicate that it is important to examine how cultural stressors may have differential impact for youth and their parents; thus, more work should examine the impact of acculturative-based family conflict for Latina mothers. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Life course models of the impact of discrimination on health and mental health outcomes posit that the pernicious effects of discrimination may not be immediate, but instead may become apparent at later stages in development. This study tests whether peer discrimination changes at particular transition points (i.e., transition to middle and high school) predict subsequent internalizing symptoms in Mexican-origin youth. In a sample of 674 Mexican-origin youth (50% female), this study used a latent change score framework to model changes in peer discrimination across time and to test whether changes in peer discrimination at 7th and 9th grades predicted greater depressive and anxiety symptoms in 12th grade controlling for 5th grade symptoms. Irrespective of longitudinal changes, greater peer discrimination in 5th grade predicted greater depressive and anxiety symptoms in 12th grade. Further, significant increases in peer discrimination from 7th to 8th grade and in 9th to 10th grade uniquely predicted greater anxiety symptoms in 12th grade. These findings suggest that longitudinal research on peer discrimination needs to take into account unique periods of risk. Future research implications are discussed.

Research has shown that taxi drivers are at risk for numerous health concerns, such as low back and leg pain, linked to their highly sedentary occupation, long work hours and stressors related to the job (e.g. low income, safety threats). The goal of this study was to explore occupational health risks and opportunities for health interventions with taxi drivers using community-based participatory research (CBPR) methods. A mixed methods approach included first a convenience sample of 19 East African taxi drivers participating in focus group discussions. Second, a convenience sample of 75 current taxi drivers (M age = 45.7 years) and 25 non-driver comparison participants (M age = 40.3 years) were recruited to complete a structured self-reported questionnaire and objective measures of health. Health education was provided alongside the research to address common health concerns and to ensure mutual benefit and an action orientation. The focus groups described numerous health concerns that drivers attributed to their occupation, including chronic pain, sleep deprivation, cardiovascular disease, diabetes, kidney disease and eye problems, as the most common. Participants offered ideas for health interventions that include workplace reform and driver education. Quantitative data indicate that 44% of drivers reported their health as 'fair' or 'poor'. Drivers were more likely to report musculoskeletal pain, less sleep, more fatigue and less physical activity as compared to non-drivers. The majority of drivers reported financial and job dissatisfaction. The research provides data to inform targeted health interventions that support the health and safety of taxi drivers., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Few studies examine how racial-ethnic peer discrimination experiences of Latinx youth vary across the race-ethnicity of the perpetrator. In a sample of 170 Latinx early adolescents (M age = 12.86 years, range = 10.33-15.23; 51% female), we identified 4 latent profiles of youth: (a) relatively low likelihood of experiencing discrimination regardless of peers' racial-ethnic group (38%; low discrimination); (b) relatively high probability of experiencing discrimination from the majority outgroup peers (33%; outgroup); (c) relatively high likelihood of experiencing discrimination from ingroup peers (14%; ingroup); (d) the highest probability of discrimination experiences across the in- and outgroup (15%; high discrimination group). Overall, Latinx youth classified in a typology characterized by a higher likelihood of experiencing discrimination from both ingroup and outgroup peers also reported the worst internalizing and externalizing symptoms relative to those in the low discrimination typology. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objectives: Familism values serve to provide key cultural scripts in Latinx families, and these values have been associated with positive psychosocial outcomes for Latinx youth (Stein et al., 2014). Yet, how familism values intersect with the experience of positive emotions remains relatively unknown. In particular, familism pride may be an important positive emotion that links familism values to positive psychosocial outcomes. To fill this gap in the literature, the current study developed a measure of familism pride and examined its unique prediction to psychosocial outcomes., Method: Self-report survey data were collected from 2 samples of Latinx emerging adults who were part of a psychology subject pool at a comprehensive university in Los Angeles designated as an Hispanic-serving institution. Sample 1 (n = 352) was 72.2% women with a mean age of 18.9 years, whereas Sample 2 was 68.6% women with a mean age of 19.3 years., Results: Factor analyses supported that familism pride was distinct from familism values (familial support, obligation, reference, respeto). Familism pride was associated with fewer depressive symptoms and greater experience of joy when controlling for familism values in both samples., Conclusions: Our study underscores the importance of examining emotional processes in the study of familism and suggests a new dimension of familism that has not received research attention. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objectives: Cultural value endorsement and ethnic-racial identity promote Latino/a adolescent positive adaptation and mitigate the negative impacts of perceived ethnic-racial discrimination. This study explored the intergenerational process of how adolescents develop these cultural characteristics in concert with their experiences of discrimination, focusing on the role of youth-reported maternal ethnic-racial socialization processes., Method: Participants included 175 Latino/a adolescent-mother dyads recruited from the 7th and 8th grades in an understudied emerging immigrant destination. We tested the effects of maternal cultural characteristics (i.e., familism, private regard, and perceived discrimination) on the same adolescent outcomes through youth-reported maternal ethnic-racial socialization practices (i.e., cultural socialization, preparation for bias, promotion of mistrust, and familism socialization, a novel construct introduced in this study)., Results: Three significant indirect pathways were identified. Higher maternal private regard was associated with both higher youth familism and higher youth private regard through greater youth-reported familism socialization, and higher maternal private regard was associated with more perceived youth discrimination through greater youth-reported preparation for bias., Conclusion: Our results highlight maternal private regard as particularly important for understanding how youth perceptions of socialization processes encourage the development of adolescent cultural characteristics and the benefit of using specific assessment tools, such as a familism socialization measure, to identify how ethnic-racial socialization processes serve as intergenerational links. Directions for future research and implications for intervention are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Given adversity associated with discrimination, it is important to identify culturally relevant factors that may protect against its harmful effects. Using latent variable interactions, this study examined the moderating effects of cultural assets on the association between multiple types of discrimination and adolescents' adjustment. Participants included 174 seventh- and eighth-grade Latino adolescents (51% girls); majority were of Mexican origin. Peer discrimination was associated with higher internalizing symptoms, whereas cultural assets predicted higher academic motivation above and beyond racial-ethnic discrimination, demonstrating a promotive effect. Adolescents' Latino cultural assets also protected against higher levels of externalizing symptoms in the context of high peer discrimination and foreigner objectification. The discussion focuses on the conceptual and applied implications of these findings., (© 2017 The Authors. Journal of Research on Adolescence © 2017 Society for Research on Adolescence.)

Given its role as the source of definitive hematopoietic cells, we sought to determine whether mutations initiated in the hemogenic endothelium would yield hematopoietic abnormalities or malignancies. Here, we find that endothelium-specific transposon mutagenesis in mice promotes hematopoietic pathologies that are both myeloid and lymphoid in nature. Frequently mutated genes included previously recognized cancer drivers and additional candidates, such as Pi4ka, a lipid kinase whose mutation was found to promote myeloid and erythroid dysfunction. Subsequent validation experiments showed that targeted inactivation of the Pi4ka catalytic domain or reduction in mRNA expression inhibited myeloid and erythroid cell differentiation in vitro and promoted anemia in vivo through a mechanism involving deregulation of AKT, MAPK, SRC, and JAK-STAT signaling. Finally, we provide evidence linking PI4KAP2, previously considered a pseudogene, to human myeloid and erythroid leukemia., (Published by Elsevier Inc.)

Centrosomes are a functionally conserved feature of eukaryotic cells that play an important role in cell division. The conserved γ-tubulin complex organizes spindle and astral microtubules, which, in turn, separate replicated chromosomes accurately into daughter cells. Like DNA, centrosomes are duplicated once each cell cycle. Although in some cell types it is possible for cell division to occur in the absence of centrosomes, these divisions typically result in defects in chromosome number and stability. In single-celled organisms such as fungi, centrosomes [known as spindle pole bodies (SPBs)] are essential for cell division. SPBs also must be inserted into the membrane because fungi undergo a closed mitosis in which the nuclear envelope (NE) remains intact. This poorly understood process involves events similar or identical to those needed for de novo nuclear pore complex assembly. Here, we review how analysis of fungal SPBs has advanced our understanding of centrosomes and NE events.

Objectives: To examine the prospective association between kidney function and three outcomes: survival to age 85 with functional independence, survival to age 85 with disability, and death before age 85., Design: Prospective study., Setting: Women's Health Initiative, conducted at 40 U.S. clinical centers., Participants: Postmenopausal women enrolled between 1993 and 1998 with baseline biomarker assessments who had the potential to reach age 85 before September 2013 (N = 7,178)., Measurements: Kidney function was measured according to estimated glomerular filtration rate (eGFR) calculated from serum creatinine collected at baseline. Outcomes were survival to age 85 with functional independence, survival with disability, or death before age 85. Disability was defined as mobility or activity of daily living limitations measured by questionnaire., Results: eGFR was greater than 90 mL/min per 1.73 m 2 in 22.7% of women, 60 to 89 mL/min per 1.73 m 2 in 66.5%, 45 to 59 mL/min per 1.73 m 2 in 8.7%, and less than 45 mL/min per 1.73 m 2 in 2.0%. Median follow-up was 15 years. Of 4,953 survivors, 3,155 reported no physical disability at age 85. Two thousand two hundred twenty-five participants died before age 85. Women with an eGFR of 90 mL/min per 1.73 m 2 or greater had 2.71 times greater odds of survival to age 85 with functional independence than of dying before 85 (95% confidence interval (CI) = 1.62-4.51) than those with an eGFR less than 45 mL/min per 1.73 m 2 , women with an eGFR of 60 to 89 mL/min per 1.73 m 2 had 3.04 times (95% CI = 1.85-5.00) greater odds, and women with an eGFR of 45 to 59 mL/min per 1.73 m 2 had 2.22 times (95% CI = 1.31-3.76) greater odds. Similar, but slightly weaker odds were seen for survival to age 85 with disability. Better kidney function was not significantly associated with greater likelihood of survival to age 85 with independent function than of surviving with disability., Conclusion: Better kidney function was associated with greater likelihood of survival to age 85 with and without disability., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

The purpose of this paper was to examine whether recollections of mothers' emotion socialization practices during childhood are linked to adult emotional well-being as indexed by depression, trait anger, and cardiac vagal tone, and whether these effects vary for African American and European American women. Participants included 251 women (128 European American; 123 African American) who ranged in age from 18 to 44 years ( M = 25 years). Multigroup confirmatory factor analyses indicated strong measurement and factor invariance across African American and European American participants. Remembered non-supportive emotion socialization was linked with elevated depressive symptoms for European American women, but not African American women and with elevated trait anger for both groups. Remembered supportive emotion socialization was linked with higher resting vagal tone for both groups. The results provide some support for the view that non-supportive emotion socialization may be more detrimental for European Americans than African Americans.

The current study aimed to identify parents' profiles of racial and emotion socialization practices, to determine if these profiles vary as a function of family income and young adult child gender, and to examine their links with young adults' emotional adaptation. Participants included 192 African American young adults (70% women) who ranged in age from 18 to 24 years (M = 19.44 years). Four maternal profiles emerged: cultural-supportive (high cultural socialization and supportive responses to children's negative emotions), moderate bias preparation (moderate preparation for bias, promotion of mistrust, and nonsupportive responses to negative emotions), high bias preparation (high preparation for bias, promotion of mistrust, and nonsupportive responses), and low engaged (low across racial and socialization constructs). Three paternal profiles emerged: multifaceted (moderate across racial and emotion socialization constructs), high bias preparation, and low engaged. Men were more likely to have mothers in the high bias preparation and to have fathers in the multifaceted or high bias preparation profiles. Individuals with higher income were more likely to have mothers in the cultural-supportive profile and to have fathers in the multifaceted profile. Young adults whose mothers fit the cultural-supportive profile or the moderate bias preparation profile had lower levels of depressive symptoms than young adults whose mothers fit the high bias preparation profile., ((c) 2015 APA, all rights reserved).)

Based on data from a sample of 120 first-generation Mexican immigrant couples collected at the start of the Great Recession in the United States, this study tested an actor-partner interdependence mediation model (APIMeM) in which spouses' perceptions of stress related to economic pressure and cultural adaptation were linked to their own and their partners' reports of marital satisfaction through spouses' depressive symptoms and marital negativity. As hypothesized, results supported indirect links between economic and cultural adaptation stressors and spouses' marital negativity and satisfaction: (1) contextual stress was associated with depressive symptoms, (2) depressive symptoms were positively associated with marital negativity for both husbands and wives and negatively associated with marital satisfaction for wives only, and (3) marital negativity was inversely associated with marital satisfaction for both spouses. Two partner effects emerged: (a) husbands' depressive symptoms were positively associated with wives' reports of marital negativity and (b) husbands' marital negativity was inversely related to wives' marital satisfaction. From these findings, we can infer that the psychological distress that arises for Mexican-origin spouses as they respond to the challenges of making ends meet during difficult economic times while they simultaneously navigate adapting to life in a new country is evidenced in their marital quality. Specifically, this study found that contextual stress external to the marital relationship was transmitted via spouses' psychological distress and negative marital exchanges to spouses' marital satisfaction. Wives' marital satisfaction was shown to be uniquely vulnerable to their own and their husbands' depressive symptoms and marital negativity.

This study examined ethnic differences in adolescent nonfatal suicidal behaviors as well as age and gender variation both across and within ethnic groups. Using a large (n = 14, 346) sample of adolescents in Grades 7 through 12, African Americans reported relatively high rates of suicidal thoughts and attempts and Southeast Asians reported high rates of suicidal thoughts. Hispanic Americans, European Americans, and Asian Americans were similar in their reports of nonfatal suicidal behaviors. Gender differences also varied across ethnicity as Southeast Asian boys (particularly older boys) reported more suicidal thoughts and attempts than Southeast Asian girls.

Membrane-type 2 matrix metalloproteinase (MT2-MMP; also called MMP15) is a membrane-bound protease that degrades extracellular matrix and activates proMMPs such as proMMP-2. MMP-2 expression in avian embryos is well documented, but it is not clear how proMMP-2 is activated during avian embryogenesis. Herein, we report that MT2-MMP mRNA is expressed in several tissues including the neural folds and epidermal ectoderm, intermediate mesoderm, pharyngeal arches, limb buds, and dermis. Several, but not all, of these tissues are known to express MMP-2. These observations suggest MT2-MMP may play a role during embryonic development not only through its own proteolytic activity but also by activating proMMP-2., (Copyright © 2012 Wiley Periodicals, Inc.)

The specification of an appropriate number of cardiomyocytes from the lateral plate mesoderm requires a careful balance of both positive and negative regulatory signals. To identify new regulators of cardiac specification, we performed a phenotype-driven ENU mutagenesis forward genetic screen in zebrafish. In our genetic screen we identified a zebrafish ctr9 mutant with a dramatic reduction in myocardial cell number as well as later defects in primitive heart tube elongation and atrioventricular boundary patterning. Ctr9, together with Paf1, Cdc73, Rtf1 and Leo1, constitute the RNA polymerase II associated protein complex, PAF1. We demonstrate that the PAF1 complex (PAF1C) is structurally conserved among zebrafish and other metazoans and that loss of any one of the components of the PAF1C results in abnormal development of the atrioventricular boundary of the heart. However, Ctr9, Cdc73, Paf1 and Rtf1, but not Leo1, are required for the specification of an appropriate number of cardiomyocytes and elongation of the heart tube. Interestingly, loss of Rtf1 function produced the most severe defects, resulting in a nearly complete absence of cardiac precursors. Based on gene expression analyses and transplantation studies, we found that the PAF1C regulates the developmental potential of the lateral plate mesoderm and is required cell autonomously for the specification of cardiac precursors. Our findings demonstrate critical but differential requirements for PAF1C components in zebrafish cardiac specification and heart morphogenesis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Zebrafish have long been utilized to study the cellular and molecular mechanisms of development by time-lapse imaging of the living transparent embryo. Here we describe a method to mount zebrafish embryos for long-term imaging and demonstrate how to automate the capture of time-lapse images using a confocal microscope. We also describe a method to create controlled, precise damage to individual branches of peripheral sensory axons in zebrafish using the focused power of a femtosecond laser mounted on a two-photon microscope. The parameters for successful two-photon axotomy must be optimized for each microscope. We will demonstrate two-photon axotomy on both a custom built two-photon microscope and a Zeiss 510 confocal/two-photon to provide two examples. Zebrafish trigeminal sensory neurons can be visualized in a transgenic line expressing GFP driven by a sensory neuron specific promoter (1). We have adapted this zebrafish trigeminal model to directly observe sensory axon regeneration in living zebrafish embryos. Embryos are anesthetized with tricaine and positioned within a drop of agarose as it solidifies. Immobilized embryos are sealed within an imaging chamber filled with phenylthiourea (PTU) Ringers. We have found that embryos can be continuously imaged in these chambers for 12-48 hours. A single confocal image is then captured to determine the desired site of axotomy. The region of interest is located on the two-photon microscope by imaging the sensory axons under low, non-damaging power. After zooming in on the desired site of axotomy, the power is increased and a single scan of that defined region is sufficient to sever the axon. Multiple location time-lapse imaging is then set up on a confocal microscope to directly observe axonal recovery from injury.