Redistribution of Transcription Factor AP-2α in Differentiating Cultured Human Epidermal Cells

Expression of the transcription factor AP-2α was examined in cultured human epidermal cells. Levels of AP-2α mRNA increased substantially after the cultures reached confluence, similar to the expression pattern of the differentiation markers involucrin and keratinocyte transglutaminase. The level of AP-2α protein in nuclear extracts declined markedly after confluence, however, along with its ability to form complexes with oligonucleotides containing the AP-2 response element. In contrast, the levels of AP-2α protein in cytoplasmic extracts increased dramatically after confluence, but these extracts had low DNA binding activity. Supershift experiments with specific antisera detected only AP-2α and not the β or γ isoforms. Examination of its localization by confocal microscopy revealed that AP-2α was primarily in the nucleus of basal cells and largely cytoplasmic in the most superficial cells. Localization was a dynamic phenomenon in that changing the medium resulted in accumulation of this transcription factor in the nucleus after several hours. Overall, the data indicate that AP-2α transcriptional activity is regulated in a differentiation-dependent manner in cultured keratinocytes and that this occurs by relocalization of the protein. Nuclear localization of the AP-2α protein in basal cells permits its accessibility to response elements in gene promoters, whereas sequestration in the cytoplasm as the differentiation program progresses curtails its transcriptional activity. This regulatory scheme may provide keratinocytes with the ability to restore AP-2 transcriptional activity rapidly by redistribution to the nucleus after receiving an appropriate growth signal, such as a medium change

Redistribution of Transcription Factor AP-2α in Differentiating Cultured Human Epidermal Cells

Expression of the transcription factor AP-2α was examined in cultured human epidermal cells. Levels of AP-2α mRNA increased substantially after the cultures reached confluence, similar to the expression pattern of the differentiation markers involucrin and keratinocyte transglutaminase. The level of AP-2α protein in nuclear extracts declined markedly after confluence, however, along with its ability to form complexes with oligonucleotides containing the AP-2 response element. In contrast, the levels of AP-2α protein in cytoplasmic extracts increased dramatically after confluence, but these extracts had low DNA binding activity. Supershift experiments with specific antisera detected only AP-2α and not the β or γ isoforms. Examination of its localization by confocal microscopy revealed that AP-2α was primarily in the nucleus of basal cells and largely cytoplasmic in the most superficial cells. Localization was a dynamic phenomenon in that changing the medium resulted in accumulation of this transcription factor in the nucleus after several hours. Overall, the data indicate that AP-2α transcriptional activity is regulated in a differentiation-dependent manner in cultured keratinocytes and that this occurs by relocalization of the protein. Nuclear localization of the AP-2α protein in basal cells permits its accessibility to response elements in gene promoters, whereas sequestration in the cytoplasm as the differentiation program progresses curtails its transcriptional activity. This regulatory scheme may provide keratinocytes with the ability to restore AP-2 transcriptional activity rapidly by redistribution to the nucleus after receiving an appropriate growth signal, such as a medium change

Concordance of Self-Report and Measured Height and Weight of College Students

Objective: This study examined associations between college students\u27 self-report and measured height and weight. Methods: Participants (N = 1,686) were 77% white, 62% female, aged 18–24 years (mean ± SD, 19.1 ± 1.1 years), and enrolled at 8 US universities. Body mass index (BMI) was calculated for self-report (via online survey); trained researchers measured height and weight and categorized them as normal (18.5 to \u3c 25), overweight (25 to \u3c 30), obese (30 to \u3c 35), and morbidly obese (≥ 35). Results: Concordance of self-report vs objectively measured BMI groups using chi-square revealed that 93% were accurate, 4% were underestimated, and 2.7% were overestimated. Pearson correlations and adjusted linear regression revealed significant associations between self-report and measured BMI (r = .97; P \u3c .001) and BMI adjusted for age, gender, and race/ethnicity (R2 = .94). Concordance was also high between BMI categories (kappa = 0.77; P \u3c .001). Conclusions and Implications: Findings provide support for the utility of self-report height and weight for survey research in college students

Children's International Polyposis (CHIP) study : a randomized, double-blind, placebo-controlled study of celecoxib in children with familial adenomatous polyposis

Objective: To evaluate the efficacy and safety of celecoxib versus placebo in the prevention and treatment of colorectal polyposis in children with familial adenomatous polyposis (FAP). Methods: In this Phase III, double-blind, randomized, placebo-controlled, multicenter trial patients aged 10-17 years with FAP were randomized to celecoxib (16 mg/kg/day) or placebo for up to 5 years. Patients underwent annual assessments, including colonoscopies, to detect the time from randomization to the earliest occurrence of >= 20 polyps (> 2 mm in size) or colorectal malignancy. The study was terminated early due to low rate of observed endpoints combined with a lower than expected enrollment rate. Descriptive results are provided. Results: Of 106 randomized patients, 55 were treated with celecoxib (mean age 12.6 years; 52.7% female) and 51 were given placebo (mean age 12.2 years; 54.9% female). Disease progression (>= 20 polyps, > 2 mm in size) was observed in seven (12.7%) and 13 (25.5%) patients, respectively. The median time to disease progression was 2.1 years in the celecoxib group and 1.1 years for placebo. No patient developed colorectal cancer. The rate of adverse events (AEs) was similar in both groups (75.5% and 72.9%, respectively). Three patients in the celecoxib group (none in the placebo group) experienced serious AEs. Conclusion: In children with FAP, celecoxib was a well-tolerated treatment that was associated with a lower rate of colorectal polyposis and a longer time to disease progression compared with placebo. Due to the low rate of observed endpoints, the long-term impact of these results could not be ascertained

Frailty Index associates with GRIN2B in two representative samples from the United States and the United Kingdom

The concept of frailty has been used in the clinical and research field for more than two decades. It is usually described as a clinical state of heightened vulnerability to poor resolution of homeostasis after a stressor event, which thereby increases the risk of adverse outcomes, including falls, delirium, disability and mortality. Here we report the results of the first genome-wide association scan and comparative gene ontology analyses where we aimed to identify genes and pathways associated with the deficit model of frailty. We used a discovery-replication design with two independent, nationally representative samples of older adults. The square-root transformed Frailty Index (FI) was the outcome variable, and age and sex were included as covariates. We report one hit exceeding genome-wide significance: the rs6765037 A allele was significantly associated with a decrease in the square-root transformed FI score in the Discovery sample (beta = -0.01958, p = 2.14E-08), without confirmation in the Replication sample. We also report a nominal replication: the rs7134291 A allele was significantly associated with a decrease in the square-root transformed FI score (Discovery sample: beta = -0.01021, p = 1.85E-06, Replication sample: beta = -0.005013, p = 0.03433). These hits represent the KBTBD12 and the GRIN2B genes, respectively. Comparative gene ontology analysis identified the pathways ‘Neuropathic pain signalling in dorsal horn neurons’ and the ‘GPCR-Mediated Nutrient Sensing in Enteroendocrine Cells’, exceeding the p = 0.01 significance in both samples, although this result does not survive correction for multiple testing. Considering the crucial role of GRIN2B in brain development, synaptic plasticity and cognition, this gene appears to be a potential candidate to play a role in frailty. In conclusion, we conducted genome-wide association scan and pathway analyses and have identified genes and pathways with potential roles in frailty. However, frailty is a complex condition. Therefore, further research is required to confirm our results and more thoroughly identify relevant biological mechanisms.</p

Reduction of Legionella spp. in water and in soil by a citrus plant extract vapor

Legionnaires disease is a severe form of pneumonia caused by Legionella spp. often isolated from environmental sources including soil and water. Legionella spp. are capable of replicating intracellularly within free living protozoa, once this has occurred Legionella spp. is particularly resistant to disinfectants. Citrus Essential Oils (EOs) vapours are effective antimicrobials against a range of microorganisms, with reductions of 5 log cells ml(-1) on a variety of surfaces. The aim of this investigation was to assess the efficacy of a citrus EO vapour against Legionella spp. in water and in soil systems. Reductions of viable cells of Legionella pneumophila, Legionella longbeachae, Legionella bozemanii and intra-amoebal culture of Legionella pneumophila (water system only), were assessed in soil and in water after exposure to a citrus EO vapour at concentrations ranging from 3.75 mg/l air to 15g/l air. Antimicrobial efficacy via different delivery systems (passive and active sintering of the vapour) was conducted in water and GC-MS analysis of the antimicrobial components (linalool, citral and β-pinene) determined. There was up to a 5 log cells ml(-1) reduction in Legionella spp. in soil after exposure to the citrus EOs vapour (15 mg/l air). The most susceptible strain in water was L. pneumophila with a 4 log cells ml(-1) reduction after 24 hrs via sintering (15 g/l air). Sintering the vapour through water increased the presence of the antimicrobial components, with a 61% increase of linalool. Therefore, the appropriate method of delivery of an antimicrobial citrus EO vapour may go some way in controlling Legionella spp. from environmental sources

Screening for Gynecologic Conditions With Pelvic Examination US Preventive Services Task Force Recommendation Statement

IMPORTANCE Many conditions that can affect women\u27s health are often evaluated through pelvic examination. Although the pelvic examination is a common part of the physical examination, it is unclear whether performing screening pelvic examinations in asymptomatic women has a significant effect on disease morbidity and mortality. OBJECTIVE To issue a new US Preventive Services Task Force(USPSTF) recommendation on screening for gynecologic conditions with pelvic examination for conditions other than cervical cancer, gonorrhea, and chlamydia, for which the USPSTF has already made specific recommendations. EVIDENCE REVIEW The USPSTF reviewed the evidence on the accuracy, benefits, and potential harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women 18 years and older who are not at increased risk for any specific gynecologic condition. FINDINGS Overall, the USPSTF found inadequate evidence on screening pelvic examinations for the early detection and treatment of a range of gynecologic conditions in asymptomatic, nonpregnant adult women. CONCLUSIONS AND RECOMMENDATION The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women. (I statement) This statement does not apply to specific disorders for which the USPSTF already recommends screening (ie, screening for cervical cancer with a Papanicolaou smear, screening for gonorrhea and chlamydia)

Clinical Skills Development in the Virtual Learning Environment: Adapting to a New World

The rapid transition to distance learning in response to the unexpected SARS-CoV-2/COVID-19 pandemic led to disruption of clinical skills development, which are typically conducted face-to-face. Consequently, faculty adapted their courses, using a multitude of active learning modalities, to meet student learning objectives in the didactic and experiential settings. Strategies and considerations to implement innovative delivery methods and address potential challenges are elucidated. Furthermore, integration of a layered learning approach may allow for more broad perspectives and allow additional interactions and feedback, which is especially necessary in the virtual environment.https://digitalcommons.chapman.edu/pharmacy_books/1025/thumbnail.jp

Emission Features and Source Counts of Galaxies in Mid-Infrared

In this work we incorporate the newest ISO results on the mid-infrared spectral-energy-distributions (MIR SEDs) of galaxies into models for the number counts and redshift distributions of MIR surveys. A three-component model, with empirically determined MIR SED templates of (1) a cirrus/PDR component (2) a starburst component and (3) an AGN component, is developed for infrared (3--120\micron) SEDs of galaxies. The model includes a complete IRAS 25\micron selected sample of 1406 local galaxies ($z \leq 0.1$; Shupe et al. 1998a). Results based on these 1406 spectra show that the MIR emission features cause significant effects on the redshift dependence of the K-corrections for fluxes in the WIRE 25\micron band and ISOCAM 15\micron band. This in turn will affect deep counts and redshift distributions in these two bands, as shown by the predictions of two evolution models (a luminosity evolution model with $L\propto (1+z)^3$ and a density evolution model with $\rho\propto (1+z)^4$). The dips-and-bumps on curves of MIR number counts, caused by the emission features, should be useful indicators of evolution mode. The strong emission features at $\sim 6$--8\micron will help the detections of relatively high redshift ($z\sim 2$) galaxies in MIR surveys. On the other hand, determinations of the evolutionary rate based on the slope of source counts, and studies on the large scale structures using the redshift distribution of MIR sources, will have to treat the effects of the MIR emission features carefully. We have also estimated a 15\micron local luminosity function from the predicted 15\micron fluxes of the 1406 galaxies using the bivariate (15\micron vs. 25\micron luminosities) method. This luminosity function will improve our understanding of the ISOCAM 15\micron surveys.Comment: 24 pages, 14 EPS figures. Accepted by Ap

Key Barriers to Medication Adherence in Survivors of Strokes and Transient Ischemic Attacks

Background: Even though medications can greatly reduce the risk of recurrent stroke, medication adherence is suboptimal in stroke survivors. Objective: To identify key barriers to medication adherence in a predominantly low-income, minority group of stroke and transient ischemic attack (TIA) survivors. Design: Cross-sectional study. Participants: Six hundred stroke or TIA survivors, age ≥ 40 years old, recruited from underserved communities in New York City. Main Measures: Medication adherence was measured using the 8-item Morisky Medication Adherence Questionnaire. Potential barriers to adherence were assessed using validated instruments. Logistic regression was used to test which barriers were independently associated with adherence. Models were additionally controlled for age, race/ethnicity, income, and comorbidity. Key Results: Forty percent of participants had poor self-reported medication adherence. In unadjusted analyses, compared to adherent participants, non-adherent participants had increased concerns about medications (26 % versus 7 %, p < 0.001), low trust in their personal doctor (42 % versus 29 %, p = 0.001), problems communicating with their doctor due to language (19 % versus 12 %, p = 0.02), perceived discrimination from the health system (42 % versus 22 %, p <0.001), difficulty accessing health care (16 % versus 8 %, p = 0.002), and inadequate continuity of care (27 % versus 20 %, p = 0.05). In the fully adjusted model, only increased concerns about medications [OR 5.02 (95 % CI 2.76, 9.11); p< 0.001] and perceived discrimination [OR 1.85 (95 % CI 1.18, 2.90); p = 0.008] remained significant barriers. Conclusions: Increased concerns about medications (related to worry, disruption, long-term effects, and medication dependence) and perceived discrimination were the most important barriers to medication adherence in this group. Interventions that reduce medication concerns have the greatest potential to improve medication adherence in low-income stroke/TIA survivors