Armored TGFßRIIDN ROR1-CAR T cells reject solid tumors and resist suppression by constitutively-expressed and treatment-induced TGFß1.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy target receptor tyrosine kinase-like orphan receptor 1 (ROR1) is broadly expressed in hematologic and solid tumors, however clinically-characterized ROR1-CAR T cells with single chain variable fragment (scFv)-R12 targeting domain failed to induce durable remissions, in part due to the immunosuppressive tumor microenvironment (TME). Herein, we describe the development of an improved ROR1-CAR with a novel, fully human scFv9 targeting domain, and augmented with TGFßRIIDN armor protective against a major TME factor, transforming growth factor beta (TGFß). METHODS: CAR T cells were generated by lentiviral transduction of enriched CD4+ and CD8+ T cells, and the novel scFv9-based ROR1-CAR-1 was compared with the clinically-characterized ROR1-R12-scFv-based CAR-2 in vitro and in vivo. RESULTS: CAR-1 T cells exhibited greater CAR surface density than CAR-2 when normalized for %CAR+, and produced more interferon (IFN)-γ tumor necrosis factor (TNF)-α and interleukin (IL)-2 in response to hematologic (Jeko-1, RPMI-8226) and solid (OVCAR-3, Capan-2, NCI-H226) tumor cell lines in vitro. In vivo, CAR-1 and CAR-2 both cleared hematologic Jeko-1 lymphoma xenografts, however only CAR-1 fully rejected ovarian solid OVCAR-3 tumors, concordantly with greater expansion of CD8+ and CD4+CAR T cells, and enrichment for central and effector memory phenotype. When equipped with TGFß-protective armor TGFßRIIDN, CAR-1 T cells resisted TGFß-mediated pSmad2/3 phosphorylation, as compared with CAR-1 alone. When co-cultured with ROR-1+ AsPC-1 pancreatic cancer line in the presence of TGFß1, armored CAR-1 demonstrated improved recovery of killing function, IFN-γ, TNF-α and IL-2 secretion. In mouse AsPC-1 pancreatic tumor xenografts overexpressing TGFß1, armored CAR-1, in contrast to CAR-1 alone, achieved complete tumor remissions, and yielded accelerated expansion of CAR+ T cells, diminished circulating active TGFß1, and no apparent toxicity or weight loss. Unexpectedly, in AsPC-1 xenografts without TGFß overexpression, TGFß1 production was specifically induced by ROR-1-CAR T cells interaction with ROR-1 positive tumor cells, and the TGFßRIIDN armor conferred accelerated tumor clearance. CONCLUSIONS: The novel fully human TGFßRIIDN-armored ROR1-CAR-1 T cells are highly potent against ROR1-positive tumors, and withstand the inhibitory effects of TGFß in solid TME. Moreover, TGFß1 induction represents a novel, CAR-induced checkpoint in the solid TME, which can be circumvented by co-expressing the TGßRIIDN armor on T cells.

Is Social Support Associated with Colorectal Cancer Care Utilization? A Multilevel Mixed-Effects Model of a Cross-Sectional Cohort Study in Vietnam.

OBJECTIVE: To investigate the relationship between the social support (SS) and colorectal cancer (CRC) care utilization of patients in the central region of Vietnam. METHODS: This was a cross-sectional cohort study in which the cohort was defined as all residential patients diagnosed with CRC in a tertiary hospital, Hue Central Hospital (HCH), in central Vietnam from 2013 to 2019. Social support was considered the main independent variable and was evaluated using the Medical Outcomes Study Social Support Survey (MOS-SSS), a self-administered 19-item SS survey. MOS-SSS is a widely used scale for assessing social support in CRC patients because it is brief, easy to use, reliable, and valid. In this study, we considered a data framework with a multilevel structure that included the patient level and duration of diagnosis as the second level. We estimated the magnitude of SS and CRC-specific treatment modalities using multilevel mixed-effects (MM) models under a hierarchical approach. RESULTS: The findings indicated that CRC care utilization rates were 89.9%, 48.5%, and 30.6% for surgical resection, chemotherapy, and radiation therapy, respectively. The overall trend of SS decreased significantly and affected the CRC care utilization. We found a positive effects of overall SS, as well as emotional and tangible support, on the number of hospitalization admissions and chemotherapy utilization. CONCLUSION: This study suggests that the use of the MOS-SSS should be continued in the long term for CRC patients to enhance medical accessibility and care utilization.

Green extraction of total phenolic and flavonoid contents from mangosteen (Garcinia mangostana L) rind using natural deep eutectic solvents.

This research combined ultrasonic-assisted extraction (UAE) and natural deep eutectic solvent (NADES) to recover phenolic and flavonoid components from mangosteen rind. The antioxidant activities were determined using DPPH, ABTS+, and hydroxyl assays. NADES prepared from lactic and 1,2-propanediol had the highest extraction efficiency based on the total flavonoid content (TFC) and phenolic contents (TPC). Single-factor experiments were employed to assess the influence of UAE conditions (liquid-to-solid ratio, temperature, water content in NADES, and time) on TFC, TPC, and antioxidant activities. NADES-based UAE conditions were optimized using response surface methodology with the Box-Behnken design model on five dependent responses (TPC, TFC, DPPH, ABTS, and OH). The optimal conditions for the lactic-1,2-Propanediol-based UAE process were 76.7 ml liquid/g solid with 30.3% of water content at 57.5 °C for 9.1 min. Scanning electron microscopy (SEM) was applied to examine the surface morphology of mangosteen rind before and after sonication. This study proposes an efficient, green, and practical approach for recovering phenolics and flavonoids from mangosteen rinds.

Polypectomy for Large Polyps with Endoscopic Mucosal Resection.

Beginning in 1955, when the saline injection was first described to prevent transmural injury during polyp fulguration, endoscopic mucosal resection (EMR) has grown exponentially, both in scope and in practice. Because EMR is an organ-preserving technique even for large polyps, this allows for comparable outcomes to surgery, but substantially improved cost savings and significantly reduced morbidity and mortality. To achieve this, however, one must master the 4 fundamental components that are critical to the success of EMR- time, team, tools, and technique. This article aims to provide a compendium of state of the art updates within the field of endoluminal resection.

Air pollution caused by phthalates and cyclic siloxanes in Hanoi, Vietnam: Levels, distribution characteristics, and implications for inhalation exposure.

Contamination status and distribution characteristics of ten phthalic acid esters (PAEs) and three cyclic volatile methyl siloxanes (CSs) were determined in the air (gas and particle) samples collected from indoor and outdoor spaces of several chemistry laboratories, offices, and homes from urban area of Hanoi, the capital city of Vietnam. Air concentrations of Σ10PAEs (median 688; range 142-2390 ng m-3) and Σ3CSs (171; not detected-1100 ng m-3) in the indoor air samples were significantly higher than those measured in the outdoor ones (Σ10PAEs: 161; 34.1-515 ng m-3 and Σ3CSs: 43.2; not detected-258 ng m-3), partly suggesting the predominance of indoor emission sources of these substances. There were significant positive correlations in total air concentrations of phthalates and siloxanes between the indoor and outdoor air samples. The most predominant phthalates were diethyl-, di-n-butyl-, diisobutyl-, and di(2-ethylhexyl) phthalate. For siloxanes, D5 and D6 were more abundant than D4 in most samples. Except for di(2-ethylhexyl)- and di-n-octyl phthalate in some locations, almost all the compounds were likely associated with gas phase than particle phase. Daily intake doses of airborne phthalates and siloxanes, and non-cancer and cancer risks of selected phthalates were estimated for different exposure groups such as adults, children, and university subjects (e.g., laboratory staff and students), indicating relatively low levels of risk.

Neural Tube Defects in Pregnancies Among Women With Diagnosed HIV Infection - 15 Jurisdictions, 2013-2017.

In May 2018, a study of birth defects in infants born to women with diagnosed human immunodeficiency virus (HIV) infection in Botswana reported an eightfold increased risk for neural tube defects (NTDs) among births with periconceptional exposure to antiretroviral therapy (ART) that included the integrase inhibitor dolutegravir (DTG) compared with other ART regimens (1). The World Health Organization* (WHO) and the U.S. Department of Health and Human Services† (HHS) promptly issued interim guidance limiting the initiation of DTG during early pregnancy and in women of childbearing age with HIV who desire pregnancy or are sexually active and not using effective contraception. On the basis of additional data, WHO now recommends DTG as a preferred treatment option for all populations, including women of childbearing age and pregnant women. Similarly, the U.S. recommendations currently state that DTG is a preferred antiretroviral drug throughout pregnancy (with provider-patient counseling) and as an alternative antiretroviral drug in women who are trying to conceive.§ Since 1981 and 1994, CDC has supported separate surveillance programs for HIV/acquired immunodeficiency syndrome (AIDS) (2) and birth defects (3) in state health departments. These two surveillance programs can inform public health programs and policy, linkage to care, and research activities. Because birth defects surveillance programs do not collect HIV status, and HIV surveillance programs do not routinely collect data on occurrence of birth defects, the related data have not been used by CDC to characterize birth defects in births to women with HIV. Data from these two programs were linked to estimate overall prevalence of NTDs and prevalence of NTDs in HIV-exposed pregnancies during 2013-2017 for 15 participating jurisdictions. Prevalence of NTDs in pregnancies among women with diagnosed HIV infection was 7.0 per 10,000 live births, similar to that among the general population in these 15 jurisdictions, and the U.S. estimate based on data from 24 states. Successful linking of data from birth defects and HIV/AIDS surveillance programs for pregnancies among women with diagnosed HIV infection suggests that similar data linkages might be used to characterize possible associations between maternal diseases or maternal use of medications, such as integrase strand transfer inhibitors used to manage HIV, and pregnancy outcomes. Although no difference in NTD prevalence in HIV-exposed pregnancies was found, data on the use of integrase strand transfer inhibitors in pregnancy are needed to understand the safety and risks of these drugs during pregnancy.

Road dust contamination by polycyclic aromatic hydrocarbons and their methylated derivatives in northern Vietnam: Concentrations, profiles, emission sources, and risk assessment.

Concentrations of unsubstituted and methylated polycyclic aromatic hydrocarbons (PAHs and Me-PAHs) were examined in road dusts from some representative areas with different land-use types in northern Vietnam, providing updated information about the occurrence, sources, and risks of these pollutants in Southeast Asian region. The Vietnamese road dusts were contaminated with low to moderate levels of PAHs and Me-PAHs as compared to those from other countries in the world. Concentrations of PAHs and Me-PAHs (Σ34PAHs) decreased in the order: urban (median 1800; range 1100-5500) ≈ industrial (1300; 550-10,000) > suburban (450; 310-1300) ≈ rural road dust (330; 210-2300 ng g-1), suggesting an urban-rural declining trend and effects of urbanization-industrialization processes in PAH emission extent in Vietnam. The profiles and diagnostic ratios of PAHs and Me-PAHs in our samples revealed that these compounds were mainly derived from pyrogenic sources rather than petrogenic sources. Traffic emissions (e.g., vehicle exhaust, tire debris, and possible leaks of fuels, oils, and lubricants) were estimated as principal sources of PAHs and Me-PAHs, especially in the urban and industrial areas. Other pyrogenic sources (e.g., coal, wood, and biomass combustion) were also existed in the industrial, suburban, and rural areas, reflecting PAH origins from thermal industrial processes, open burning of agricultural by-products, and domestic energy utilization. Persons working outdoors and children in the urban and industrial areas were estimated to receive higher intake doses of PAHs and Me-PAHs, which were one to two orders of magnitude higher than those estimated for other groups. Except for potential cancer risk estimated for the occupational groups in the industrial area under the worst exposure scenarios, the non-cancer and cancer risk levels were generally acceptable; however, more comprehensive risk assessment considering other exposure pathways (e.g., inhalation and diet) is needed.

Multiresidue Pesticides Analysis of Vegetables in Vietnam by Ultrahigh-Performance Liquid Chromatography in Combination with High-Resolution Mass Spectrometry (UPLC-Orbitrap MS).

An ultrahigh-performance liquid chromatography in combination with high-resolution mass spectrometry Thermo Q-Extractive Focus Orbitrap MS has been introduced for analysis of multiclass pesticides in vegetable samples collected in Hanoi, Vietnam. Multiclass pesticides were separated on the Thermo Hypersil Gold PFP column utilizing a gradient of the mobile phase consisting of 5 mM ammonium formate, 0.1% formic acid in deionized water, and methanol. The target analytes were detected in the full-scan mode on Thermo Scientific Q-Exactive Focus Orbitrap MS for quantitation at the optimum operating conditions. These conditions included, but not limit to, the resolution of 70000 at the full width at half maximum in both positive and negative mode, mass range from 80 to 1000 m/z, and optimized parameters for the heated electrospray ionization source. The identification of the analytes in real samples was based on retention times, mass to charge ratios, mass accuracies, and MS/MS spectra at the confirmation mode with the inclusion list of target analytes. The mass accuracies of target analytes were from -4.14 ppm (dinotefuran) to 1.42 ppm (cinosulfuron) in the neat solvent and from -3.91 ppm (spinosad D) to 1.29 ppm (cinosulfuron) in the matrix-matched solution. Target analytes in the vegetable-based matrix were extracted by the QuEChERS method. Some critical parameters of the analytical method such as linearity, repeatability, limit of detection, and limit of quantitation have been evaluated and implemented. Excellent LOD and LOQ of the developed method were achieved at the range of 0.04-0.85 and 0.13-2.9 µg·kg-1, respectively. Intraday and interday repeatability of the analytical signal (peak area, n=6) of the developed method were below 3% and 10%, correspondingly. The matrix effect, extraction recovery, and overall recovery were fully investigated by spiking experiments. Experimental results demonstrated that the ionization suppression or enhancement was the main contribution on the overall recoveries of target analytes. Finally, the in-house validated method was applied to pesticides screening in vegetables samples in local villages in Hanoi, Vietnam. The concentrations of all target analytes were below limit of quantitation and lower than US-FDA or EU maximum residue levels.

Gastroschisis Trends and Ecologic Link to Opioid Prescription Rates - United States, 2006-2015.

Prevalence of gastroschisis, a serious birth defect of the abdominal wall resulting in some of the abdominal contents extending outside the body at birth, has been increasing worldwide (1,2). Gastroschisis requires surgical repair after birth and is associated with digestive and feeding complications during infancy, which can affect development. Recent data from 14 U.S. states indicated an increasing prevalence of gastroschisis from 1995 to 2012 (1). Young maternal age has been strongly associated with gastroschisis, but research suggests that risk factors such as smoking, genitourinary infections, and prescription opioid use also might be associated (3-5). Data from 20 population-based state surveillance programs were pooled and analyzed to assess age-specific gastroschisis prevalence during two 5-year periods, 2006-2010 and 2011-2015, and an ecologic approach was used to compare annual gastroschisis prevalence by annual opioid prescription rate categories. Gastroschisis prevalence increased only slightly (10%) from 2006-2010 to 2011-2015 (prevalence ratio = 1.1, 95% confidence interval [CI] = 1.0-1.1), with the highest prevalence among mothers aged <20 years. During 2006-2015, the prevalence of gastroschisis was 1.6 times higher in counties with high opioid prescription rates (5.1 per 10,000 live births; CI = 4.9-5.3) and 1.4 times higher where opioid prescription rates were medium (4.6 per 10,000 live births; CI = 4.4-4.8) compared with areas with low prescription rates (3.2 per 10,000 live births; CI = 3.1-3.4). Public health research is needed to understand factors contributing to the association between young maternal age and gastroschisis and assess the effect of prescription opioid use during pregnancy on this pregnancy outcome.

Filler Migration and Granuloma Formation After Gluteal Augmentation with Free-silicone Injections.

Gluteal augmentation may be performed using a variety of techniques, including implant-based, autologous fat grafting, local flaps, impermanent filler injection, or, as in this case, by way of permanent filler injection with free-silicone. Of these, free-silicone injections carry one of the highest complication rates, specifically regarding migration of the filler material from the native injection site and induction of painful reactive soft tissue changes at the new filler location. A radiologist providing this diagnosis may assist the clinician, who often cannot obtain a history of illicit silicone injection for gluteal augmentation unless the suspicion is raised. Presented here is a case of painful filler migration to the knee with granuloma formation after free-silicone gluteal injection.

Tumor Uptake of 64Cu-DOTA-Trastuzumab in Patients with Metastatic Breast Cancer.

The goal of this study was to characterize the relationship between tumor uptake of 64Cu-DOTA-trastuzumab as measured by PET/CT and standard, immunohistochemistry (IHC)-based, histopathologic classification of human epidermal growth factor receptor 2 (HER2) status in women with metastatic breast cancer (MBC). Methods: Women with biopsy-confirmed MBC and not given trastuzumab for 2 mo or more underwent complete staging, including 18F-FDG PET/CT. Patients were classified as HER2-positive (HER2+) or -negative (HER2-) based on fluorescence in situ hybridization (FISH)-supplemented immunohistochemistry of biopsied tumor tissue. Eighteen patients underwent 64Cu-DOTA-trastuzumab injection, preceded in 16 cases by trastuzumab infusion (45 mg). PET/CT was performed 21-25 (day 1) and 47-49 (day 2) h after 64Cu-DOTA-trastuzumab injection. Radiolabel uptake in prominent lesions was measured as SUVmax Average intrapatient SUVmax (pt) was compared between HER2+ and HER2- patients. Results: Eleven women were HER2+ (8 immunohistochemistry 3+; 3 immunohistochemistry 2+/FISH amplified), whereas 7 were HER2- (3 immunohistochemistry 2+/FISH nonamplified; 4 immunohistochemistry 1+). Median pt for day 1 and day 2 was 6.6 and 6.8 g/mL for HER 2+ and 3.7 and 4.3 g/mL for HER2- patients (P < 0.005 either day). The distributions of pt overlapped between the 2 groups, and interpatient variability was greater for HER2+ than HER2- disease (P < 0.005 and 0.001, respectively, on days 1 and 2). Conclusion: By 1 d after injection, uptake of 64Cu-DOTA-trastuzumab in MBC is strongly associated with patient HER2 status and is indicative of binding to HER2. The variability within and among HER2+ patients, as well as the overlap between the HER2+ and HER2- groups, suggests a role for 64Cu-DOTA-trastuzumab PET/CT in optimizing treatments that include trastuzumab.

Molecularly Imprinted Porous Monolithic Materials from Melamine-Formaldehyde for Selective Trapping of Phosphopeptides.

Thirty-five melamine-formaldehyde (MF) monolithic materials with bimodal pore distributions were synthesized in fused silica capillaries by catalyst-free polycondensation, starting with an aqueous MF precondensate, using acetonitrile as the macroporogen and a variety of aliphatic polyethers and triblock copolymeric surfactants as porogens and mesoporogens, respectively. By varying the prepolymer composition and the type and molecular weight of the polymeric porogen components, a library of porous monolithic materials was produced, covering a range of meso- and macroporous properties. A multivariate evaluation revealed that the amount of surfactant was the strongest contributor to specific surface area and pore volume and to the inversely related mesopore size, whereas the macropore dimensions were controlled mainly by the amount of aliphatic polyether porogen. One of these capillary monoliths, chosen based on the combination of meso- and macropores providing optimal percolative flow and accessible surface area, was synthesized in the presence of N-Fmoc and O-Et protected phosphoserine and phosphotyrosine to prepare molecularly imprinted monoliths with surface layers selective for phosphopeptides. These imprinted monoliths were characterized alongside nonimprinted monoliths by a variety of techniques and finally evaluated by liquid chromatography-mass spectrometry in the capillary format to assess their abilities to trap and release phosphorylated amino acids and peptides from partly aqueous media. Selective enrichment of phosphorylated targets was demonstrated, suggesting that these materials could be useful as trapping media in affinity-based phosphoproteomics.

The Human Leukocyte Antigen (HLA)-B27 Peptidome in Vivo, in Spondyloarthritis-susceptible HLA-B27 Transgenic Rats and the Effect of Erap1 Deletion.

HLA-B27 is a class I major histocompatibility (MHC-I) allele that confers susceptibility to the rheumatic disease ankylosing spondylitis (AS) by an unknown mechanism. ERAP1 is an aminopeptidase that trims peptides in the endoplasmic reticulum for binding to MHC-I molecules. ERAP1 shows genetic epistasis with HLA-B27 in conferring susceptibility to AS. Male HLA-B27 transgenic rats develop arthritis and serve as an animal model of AS, whereas female B27 transgenic rats remain healthy. We used large scale quantitative mass spectrometry to identify over 15,000 unique HLA-B27 peptide ligands, isolated after immunoaffinity purification of the B27 molecules from the spleens of HLA-B27 transgenic rats. Heterozygous deletion of Erap1, which reduced the Erap1 level to less than half, had no qualitative or quantitative effects on the B27 peptidome. Homozygous deletion of Erap1 affected approximately one-third of the B27 peptidome but left most of the B27 peptidome unchanged, suggesting the possibility that some of the HLA-B27 immunopeptidome is not processed in the presence of Erap1. Deletion of Erap1 was permissive for the AS-like phenotype, increased mean peptide length and increased the frequency of C-terminal hydrophobic residues and of N-terminal Ala, Ser, or Lys. The presence of Erap1 increased the frequency of C-terminal Lys and Arg, of Glu and Asp at intermediate residues, and of N-terminal Gly. Several peptides of potential interest in AS pathogenesis, previously identified in human cell lines, were isolated. However, rats susceptible to arthritis had B27 peptidomes similar to those of non-susceptible rats, and no peptides were found to be uniquely associated with arthritis. Whether specific B27-bound peptides are required for AS pathogenesis remains to be determined. Data are available via ProteomeXchange with identifier PXD005502.

Occurrence of phthalate diesters (phthalates), p-hydroxybenzoic acid esters (parabens), bisphenol A diglycidyl ether (BADGE) and their derivatives in indoor dust from Vietnam: Implications for exposure.

Phthalate diesters (phthalates), esters of p-hydroxybenzoic acid (parabens), and bisphenol A diglycidyl ether (BADGE) are used in personal care products, food packages, household products, or pharmaceuticals. These compounds possess endocrine-disrupting potentials and have been reported to occur in the environment. Nevertheless, no previous studies have reported the occurrence of these compounds in indoor dust from Vietnam. In this study, nine phthalates, six parabens, and four BADGEs were determined in indoor dust samples collected from Hanoi, Hatinh, Hungyen, and Thaibinh, in Vietnam. Total concentrations of phthalates, parabens, and BADGEs in indoor dust ranged from 3440 to 106,000 ng/g (median: 22,600 ng/g), 40-840 ng/g (median: 123 ng/g), and 23 to 1750 ng/g (median: 184 ng/g), respectively. Based on the measured median concentration of phthalates, parabens, and BADGEs in indoor dust, we estimated human exposure doses to these compounds through indoor dust ingestion for various age groups. The exposure doses to phthalates, parabens, and BADGEs decreased with age and ranged from 19.4 to 90.4 ng/kg-bw/d, 0.113-0.528 ng/kg-bw/d, and 0.158-0.736 ng/kg-bw/d, respectively. This is the first study on the occurrence and human exposure of phthalates, parabens, and BADGEs in indoor dust from Vietnam.

The Association Between the Medical Home and Pediatric Developmental Screening Among US Children Five Years and Younger: Results From the 2007 National Survey of Children's Health.

OBJECTIVES: The medical home is associated with key healthcare services. We assessed its association with the pediatric developmental screening among United States (US) children less than or equal to five years. METHODS: The 2007 national survey of children's health data was analyzed using state clusters, and pediatric developmental screening probability was modeled as a function of the medical home. RESULTS: Only 19.5% of US children received pediatric developmental screening, and crosstabs showed a null medical home association. Based on medical home status, adjusted state models showed much variation in pediatric developmental screening odds. A random intercept and slope model had the best fit. The medical home increased pediatric developmental screening odds by 24% (1.10, 1.38). CONCLUSIONS: The pediatric developmental screening rate and the medical home association are partially influenced by an individual's state. A multilevel model including state level predictors will help illuminate factors that promote healthcare service acquisition. This knowledge will enhance policy development in public and private sector health programs.

Association between smoking cessation interventions during prenatal care and postpartum relapse: results from 2004 to 2008 multi-state PRAMS data.

Cigarette smoking is a serious global public health issue, and is particularly harmful to the maternal and child population. The study aimed to determine if there was an association between smoking cessation intervention during pregnancy and postpartum smoking relapse, and to define a time trend of postpartum smoking relapse after delivery. Data from the 2004-2008 pregnancy risk assessment monitoring systems of Colorado, Maine, Ohio, and Washington were analyzed. Logistic regression was used to define the association between smoking cessation intervention and postpartum smoking relapse, and to identify trend of postpartum smoking relapse. Analyses were done using SAS-Callable SUDAAN v.10.0 and Mplus v.6.0. Among the 2,938 women in the study the relapse rate was 48 %. It was 45 % among those without intervention, 58 % among those who received only counseling, and 57 % among those who received both counseling with treatment and/or referral. The rate was 42, 61, and 67 % among women whose infants were at 2-3, 4-5, and 6 months or more, respectively. Adjusted logistic regression models showed a trend of increased smoking relapse, but did not indicate an association between smoking cessation intervention and smoking relapse. Rates of smoking relapse were high and increased by time after delivery. Smoking cessation intervention during pregnancy may not be successful at preventing postpartum smoking relapse.

A community-based participatory research approach to understanding pap testing adherence among Vietnamese American immigrants.

OBJECTIVE: To explore factors potentially influencing Pap testing practices among Vietnamese American immigrant women (VIW, foreign-born) and describe their awareness of cervical cancer screening resources in their community. DESIGN: Descriptive study guided by the ecological model and community-based participatory research principles. SETTING: Portland, Oregon, metropolitan area. PARTICIPANTS: Vietnamese American immigrant women (211) who were age 21 and older. METHODS: We used descriptive statistics and logistic regression analyses to analyze a self-administered questionnaire that was pretested and translated using a team approach. RESULTS: Approximately 74% of VIW who completed the survey reported at least one Pap test, and 69% reported Pap testing history adherent to national guidelines. The factor most strongly associated with Pap testing receipt was suggestion from a friend, followed by longer residency in the United States, lower perceived common barriers, and lower perceived cultural barriers, for example, lack of family support and use of Eastern/Asian medicine. The factor most strongly associated with guideline adherence was having health insurance, followed by a recommendation from a physician or nurse practitioner. Only 11% of VIW knew where to obtain a free or low-cost Pap tests. CONCLUSION: Nurses can influence rates of Pap testing among VIW by providing health education through outreach programs targeted at lay health workers and their social networks, identifying at-risk patients such as recently immigrated women, reducing perceived common and cultural barriers to Pap testing, and helping women seek alternative payment options if they lack health insurance. Primary health care providers should be reminded of their essential role in increasing Pap testing adherence.

Infant secondhand smoke exposure in Louisiana, 1998-2004: trend and high risk population.

PURPOSES: To evaluate the trend of infant secondhand smoke exposure (ISHSE) at home from 1998 to 2004 and define high risk infants exposed to secondhand smoke. METHODS AND SUBJECTS: 1998-2004 Louisiana Pregnancy Risk Assessment Monitoring System data were used. Logistic regression was applied to determine the trend of ISHSE and define variables associated with ISHSE. RESULTS: Adjusted annual percent increase of odds of ISHSE was 9.0% (p = .0020) among blacks. Adjusted annual percent decrease of odds of ISHSE was 5.0% (p = .0084) among whites. Adjusted odds of ISHSE was higher among women with characteristics as follows: currently smoked, age < 20 years, < high school education, unmarried, never breastfed their infants, had term delivery or deliveries paid for by Medicaid. CONCLUSIONS: Prevalence of ISHSE increased in blacks and decreased in whites between 1998 and 2004. Smoking status, maternal age, education, marital status, delivery payment source, delivery status, and breastfeeding status were associated with ISHSE.

FGF inhibits the activity of the cyclin B1/CDK1 kinase to induce a transient G2arrest in RCS chondrocytes.

Fibroblast growth factors (FGFs) negatively regulate long bone development by inhibiting the proliferation of chondrocytes that accumulate in the G1 phase of the cycle following FGF treatment. Here we report that FGF also causes a striking but transient delay in mitotic entry in RCS chondrocytes by inactivating the cyclin B1-associated CDK1(CDC2) kinase. As a consequence of this inactivation, cells accumulate in the G2 phase of the cycle for the first 4-6 hours of the treatment. Cyclin B1/CDK1 activity is then restored and cells reach a G1 arrest. The reduced cyclin B1/CDK1 activity was accompanied by increased CDK1 inhibitory phosphorylation, likely caused by increased activity and expression of the Myt1 kinase. FGF1 also caused dephosphorylation of the CDC25C phosphatase, that however appears due the inactivation of cyclin B1/CDK1 complex in the CDK1 feedback loop, and not the activation of specific phosphatases. the inactivation of the cyclin B1/CDK1 complex is a direct effect of FGF signaling, and not a consequence of the G2 arrest as it can be observed also in cells blocked at mitosis by Nocodazole. The Chk1 and AtM/ATR kinase are known to play essential roles in the G2 checkpoint induced by DNA damage/genotoxic stress, but inhibition of Chk1 or ATM/ATR not only did not prevent, but rather potentiated the FGF-induced G2 arrest. Additionally our results indicate that the transient G2 arrest is induced by FGF in RCS cell through mechanisms that are independent of the G1 arrest, and that the G2 block is not strictly required for the sustained G1 arrest but may provide a pausing mechanism that allows the FGF response to be fully established.

Activation-induced degradation of FLIP(L) is mediated via the phosphatidylinositol 3-kinase/Akt signaling pathway in macrophages.

Cellular FLIP (Flice-like inhibitory protein) is critical for the protection against death receptor-mediated cell apoptosis. In macrophages, FLIP long (FLIP(L)) and FLIP short (FLIP(S)) mRNA was induced by tumor necrosis factor (TNF) alpha, mediated through NF-kappaB. However, we observed TNFalpha reduced the protein level of FLIP(L), but not FLIP(S), at 1 and 2 h. Similar results were observed with lipopolysaccharide. The reduction of FLIP(L) by TNFalpha was not mediated by caspase 8, or through JNK or Itch, but was suppressed by inhibition of the phosphatidylinositol 3-kinase/Akt pathway employing chemical inhibitors, a dominant negative Akt-1, or Akt-1 small interfering RNA. The reduction of FLIP(L) resulted in the short term induction of caspase 8-like activity, which augmented NF-kappaB activation. A co-immunoprecipitation assay demonstrated that Akt-1 physically interacts with FLIP(L). Moreover, TNFalpha enhanced FLIP(L) serine phosphorylation, which was increased by activated Akt-1. Serine 273, a putative Akt-1 phosphorylation site in FLIP(L), was critical for the activation-induced reduction of FLIP(L). Thus, these observations document a novel mechanism where by TNFalpha facilitates the reduction of FLIP(L) protein, which is dependent on the phosphatidylinositol 3-kinase/Akt signaling.