Exploring how workplace and social policies relate to caregivers' financial strain.

Informal caregiving is a critical component of the US long-term care system, but can have significant negative impacts on caregiver employment, finances, and well-being. An online survey of Colorado caregivers was piloted in 2016-17 to explore whether workplace and social policies such as access to paid family leave and public health insurance can buffer the negative financial impacts of caregiving and help caregivers to remain in the workforce. Using standardized measures, the survey assessed caregivers' employment and financial status, well-being (physical and mental health, caregiver strain, benefits of caregiving), access to workplace supports, and covariates (e.g., caregiver demographics, health, social support, and service utilization). Ninety-five caregivers, recruited through community agency partners, completed the survey. Respondents were predominately female (89%), middle-aged (M = 57), non-Hispanic White (64%) or Latino/a (22%), and caring for a parent (40%) or spouse (30%) for over one year. Half (51%) reported working full- or part-time jobs, while 16.4% had stopped working because of caregiving. In multivariate regression modeling, predictors of financial strain included the care recipients' financial strain and the caregiver's reduction or ceasing of work. Medicare may be protective to minimize caregivers' need to reduce or cease work. Implications for caregivers' ability to stay engaged in the workforce and prepare for their own retirement are explored.

Decisions about overdraft coverage: Disclosure design and personal finances.

Policymakers often require disclosures to help consumers make informed decisions, despite considerable debate over disclosures' effectiveness. Traditional accounts argue that consumers with stable preferences use disclosures to become informed. In contrast, behavioral research suggests that consumers may be inattentive or construct preferences in the moment. We contrast these accounts in the context of overdraft, where consumers can "opt in" to coverage and fees. In Study 1, we use conjoint analysis to assess perceptions of whether consumers in varying circumstances should opt in. Both overdraft program characteristics (including fees) and consumers' personal financial characteristics (e.g., having a financial buffer) matter. In Study 2, we compare three overdraft disclosures, finding variation in the proportion of consumers who make an active choice (15%-65%) and limited effects on comprehension and opt-in rates. In Study 3, we augment overdraft disclosures with text about personal financial characteristics. These disclosures increase active choice without detrimental effects on comprehension. Together, our studies support a constructed preferences account and highlight specific benefits of reminding consumers about the match between financial products and their personal situations. We discuss implications for financial disclosures and overdraft policy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Pre-Birth Household Challenges Predict Future Child's School Readiness and Academic Achievement.

Early developmental success and school readiness strongly influence future skill development, occupational opportunities, and health. Therefore, it is critical to identify and address early determinants of school readiness for supporting children's overall well-being and success. In this retrospective cohort study, we examined the effects of pre-birth household challenges, such as homelessness or experiences of intimate partner violence, on children's early school readiness. We linked data from the Alaska 2009-2011 Pregnancy Risk Assessment Monitoring System (PRAMS) to administrative and education records through 2019. Education records included kindergarten developmental scores, third grade reading assessments, and attendance records. Generalized linear models with Quasi-Poisson distributions for each outcome of interest examined the predictive value of pre-birth household challenges on the risks of not meeting school readiness expectations. We found that experiencing higher numbers of pre-birth household challenges was related to higher risk of the child not meeting developmental and reading proficiency and having chronic absenteeism. These results suggest that it is imperative support systems for pregnant persons and their families be introduced as soon as possible in pre-natal care routines to address current pre-birth household stressors and prevent future challenges. Such early prevention efforts are needed to ensure the best possible developmental start for children.

The molecular scaffold kinase suppressor of Ras 1 is a modifier of RasV12-induced and replicative senescence.

In primary mouse embryo fibroblasts (MEFs), oncogenic Ras induces growth arrest via Raf/MEK/extracellular signal-regulated kinase (ERK)-mediated activation of the p19ARF/p53 and INK4/Rb tumor suppressor pathways. Ablation of these same pathways causes spontaneous immortalization in MEFs, and oncogenic transformation by Ras requires ablation of one or both of these pathways. We show that Kinase Suppressor of Ras 1 (KSR1), a molecular scaffold for the Raf/MEK/ERK cascade, is necessary for RasV12-induced senescence, and its disruption enhances primary MEF immortalization. RasV12 failed to induce p53, p19ARF, p16INK4a, and p15INK4b expression in KSR1-/- MEFs and increased proliferation instead of causing growth arrest. Reintroduction of wild-type KSR1, but not a mutated KSR1 construct unable to bind activated ERK, rescued RasV12-induced senescence. On continuous culture, deletion of KSR1 accelerated the establishment of spontaneously immortalized cultures and increased the proportion of cultures escaping replicative crisis. Despite enhancing escape from both RasV12-induced and replicative senescence, however, both primary and immortalized KSR1-/- MEFs are completely resistant to RasV12-induced transformation. These data show that escape from senescence is not necessarily a precursor for oncogenic transformation. Furthermore, these data indicate that KSR1 is a member of a unique class of proteins whose deletion blocks both senescence and transformation.

Clinical instructors' perceptions of behaviors that comprise entry-level clinical performance in physical therapist students: a qualitative study.

BACKGROUND AND PURPOSE: The purpose of this study was to qualitatively explore clinical instructors' (CIs) perceptions of students' behaviors that comprise entry-level clinical performance, as well as how those perceptions were integrated into their decision making. SUBJECTS: The participants were 21 physical therapists who were CIs for physical therapist students. METHODS: Using a grounded theory approach, we conducted interviews, asking the question, "What is it about students' performance that makes you see them as entry-level therapists?" We determined common themes among the interviews and developed a schema to explain the decision-making process. RESULTS: Participants identified 7 attributes that, when demonstrated to a sufficient degree, illustrated to them students' ability to practice at the entry level. Those attributes were knowledge, clinical skills, safety, clinical decision making, self-directed learning, interpersonal communication, and professional demeanor. Participants viewed these attributes in concert to form a subjective "gut feeling" that a student demonstrated entry-level performance. A final theme emerged suggesting a definition of entry-level performance as "mentored independence." DISCUSSION AND CONCLUSION: Participants reported evaluating students' performance based on attributes similar to those suggested by the American Physical Therapy Association's Physical Therapist Clinical Performance Instrument and previous research. However, subjectivity also was involved in their decision about whether students were able to practice at the entry level. Participants also concluded that entry-level students need not be independent in all clinical situations.

Genotoxic stress leads to centrosome amplification in breast cancer cell lines that have an inactive G1/S cell cycle checkpoint.

Centrosome amplification plays a key role in the origin of chromosomal instability during cancer development and progression. In this study, breast cancer cell lines with different p53 backgrounds were used to investigate the relationship between genotoxic stress, G(1)/S cell cycle checkpoint integrity, and the development of centrosome amplification. Introduction of DNA damage in the MCF-7 cell line by treatment with hydroxyurea (HU) or daunorubicin (DR) resulted in the arrest of both G(1)/S cell cycle progression and centriole duplication. In these cells, which carry functional p53, HU treatment also led to nuclear accumulation of p53 and p21(WAF1), retinoblastoma hypophosphorylation, and downregulation of cyclin A. MCF-7 cells carrying a recombinant dominant-negative p53 mutant (vMCF-7(DNp53)) exhibited a shortened G(1) phase of the cell cycle and retained a normal centrosome phenotype. However, these cells developed amplified centrosomes following HU treatment. The MDA-MB 231 cell line, which carries mutant p53 at both alleles, showed amplified centrosomes at the outset, and developed a hyperamplified centrosome phenotype following HU treatment. In cells carrying defective p53, the development of centrosome amplification also occurred following treatment with another DNA damaging agent, DR. Taken together, these findings demonstrate that loss of p53 function alone is not sufficient to drive centrosome amplification, but plays a critical role in this process following DNA damage through abrogation of the G(1)/S cell cycle checkpoint. Furthermore, these studies have important clinical implications because they suggest that breast cancers with compromised p53 function may develop centrosome amplification and consequent chromosomal instability following treatment with genotoxic anticancer drugs.

Using Advanced Continuous Simulation Language (ACSL) to simulate, solve, and fit mathematical models in nutrition.

The ACSL programs (AEgis Technologies, 2000a, b) are fairly easy to use and provide a good combination of canned programming with the flexibility to do more, if one is willing to learn the language (for Fortran and m files). The manuals are fairly easy to understand but are not detailed enough. The manuals are geared toward operating the software. For the Optimize software, the best references are the Simusolv manuals (Steiner et al., 1990). ACSL also provides an interface (Open API or ACSL Server) which can be purchased separately. The interface allows compiled models to be distributed and run as independent programs with Visual Basic or C/C++. For models built with the Graphic Modeler, the interface is shareware.

Challenging the assumptions in estimating protein fractional synthesis rate using a model of rodent protein turnover.

Published estimates of protein fractional synthetic rate vary widely (Johnson et al., 1999a). Contributing to the large standard deviation for FSR are physiological and methodological differences that do not account for changes in specific radioactivities of I, E, T, and P. Current methods for estimating FSR are based on four assumptions which may not be valid. The first assumption, that the free amino acid pool is homogenous and reflects the specific radioactivity of the true precursor pool (aminoacyl tRNA), can cause FSR estimates to increase by up to 8%/d. The second assumption, that recycling has an insignificant effect on FSR estimates, could result in decreases in estimates of FSR from 10 to 20%/d. The third assumption, that the protein pool is homogeneous and will not change over time, results in a 4-10%/d change using the flooding dose method. The fourth assumption, that growth will not affect estimated FSR over a short experimental time, is true if aminoacyl tRNA specific radioactivity is used to estimate FSR. Otherwise, estimates can vary 4-5%/d. Although specific radioactivity of aminoacyl tRNA is difficult to measure, the first and fourth assumptions are valid if aminoacyl tRNA specific radioactivity is used. Using a model of protein turnover, as described in this paper, to interpret specific radioactivity data allows the inclusion of all four assumptions and the potential to better quantify changes in FSR under different physiological conditions.

Migraine in students of a US medical school.

BACKGROUND AND OBJECTIVES: The study's aim was to determine migraine prevalence, severity, and educational impact in medical students. METHODS: A 23-item survey of all medical students of one US medical school addressed migraine frequency, triggers, pattern and severity of symptoms, medication use, impact on educational activities and career choices. RESULTS: The response rate was 48% (359 students). Eighty-nine (24.8%) self-reported migraine, and all were confirmed by reported symptoms. Of these students, 54% had a physician-confirmed diagnosis. Migraine prevalence was 35% in women and 14.1% in men. About half of migraineurs reported one or more attacks monthly. Stress and sleep disturbances were the most common triggers. Pain severity was rated 7 or higher on a 10-point scale by 73%. NSAIDs were the most common medications used. Only 13% used prophylaxis. More than 80% reported reduced productivity during migraine, but 76% felt obliged to attend educational activities despite symptoms. A total of 81% of students did not endorse informing faculty about migraine status, and 95% would not disclose it in residency application. Migraine was not a factor in choice of medical specialty or specific residency program. CONCLUSIONS: Migraine is common in medical students, especially women. Only half have consulted a physician for migraine, and students may be using suboptimal treatments. Although more than half experience severe symptoms that impair performance, the majority attend educational sessions during migraine attacks, and they believe this is expected. Students are unwilling to disclose migraine status to faculty or during application to residency. Migraine does not influence career choices.

Caveolin-1 is required for kinase suppressor of Ras 1 (KSR1)-mediated extracellular signal-regulated kinase 1/2 activation, H-RasV12-induced senescence, and transformation.

The molecular scaffold kinase suppressor of Ras 1 (KSR1) regulates the activation of the Raf/MEK/extracellular signal-regulated kinase (ERK) signal transduction pathway. KSR1 disruption in mouse embryo fibroblasts (MEFs) abrogates growth factor-induced ERK activation, H-Ras(V12)-induced replicative senescence, and H-Ras(V12)-induced transformation. Caveolin-1 has been primarily described as a major component of the coating structure of caveolae, which can serve as a lipid binding adaptor protein and coordinates the assembly of Ras, Raf, MEK, and ERK. In this study, we show that KSR1 interacts with caveolin-1 and is responsible for MEK and ERK redistribution to caveolin-1-rich fractions. The interaction between KSR1 and caveolin-1 is essential for optimal activation of ERK as a KSR1 mutant unable to interact with caveolin-1 does not efficiently mediate growth factor-induced ERK activation at the early stages of pathway activation. Furthermore, abolishing the KSR1-caveolin-1 interaction increases growth factor demands to promote H-Ras(V12)-induced proliferation and has adverse effects on H-Ras(V12)-induced cellular senescence and transformation. These data show that caveolin-1 is necessary for optimal KSR1-dependent ERK activation by growth factors and oncogenic Ras.

KSR1 is required for cell cycle reinitiation following DNA damage.

KSR1 (kinase suppressor of Ras 1) is a molecular scaffold and positive regulator of the Raf/MEK/ERK phosphorylation cascade. KSR1 is required for maximal ERK activation induced by growth factors and by some cytotoxic agents. We show here that KSR1 is also required for maximal ERK activation induced by UV light, ionizing radiation, or the DNA interstrand cross-linking agent mitomycin C (MMC). We further demonstrate a role for KSR1 in the reinitiation of the cell cycle and proliferation following cell cycle arrest induced by MMC. Cells lacking KSR1 underwent but did not recover from MMC-induced G(2)/M arrest. Expression of KSR1 allowed KSR1(-/-) cells to re-enter the cell cycle following MMC treatment. However, cells expressing a mutated form of KSR1 unable to bind ERK did not recover from MMC-induced cell cycle arrest, demonstrating the requirement for the KSR1-ERK interaction. In addition, constitutive activation of ERK was not sufficient to promote cell cycle reinitiation in MMC-treated KSR1(-/-) cells. Only cells expressing KSR1 recovered from MMC-induced cell cycle arrest. Importantly, MMC-induced DNA damage was repaired in KSR1(-/-) cells, as determined by resolution of gamma-H2AX-containing foci. These data indicate that cell cycle reinitiation is not actively signaled in the absence of KSR1, even when DNA damage has been resolved. These data reveal a specific role for the molecular scaffold KSR1 and KSR1-mediated ERK signaling in the cellular response to DNA interstrand cross-links.