The impact of breast density notification on psychosocial outcomes in racial and ethnic minorities: A systematic review.

BACKGROUND: High breast density is an independent risk factor for breast cancer and decreases the sensitivity of mammography. This systematic review synthesizes the evidence on the impact of breast density (BD) information and/or notification on women's psychosocial outcomes among women from racial and ethnic minority groups. METHODS: A systematic search was performed in March 2023, and the articles were identified using CINHAL, Embase, Medline, and PsychInfo databases. The search strategy combined the terms "breast", "density", "notification" and synonyms. The authors specifically kept the search terms broad and did not include terms related to race and ethnicity. Full-text articles were reviewed for analysis by race, ethnicity and primary language of participants. Two authors evaluated the eligibility of studies with verification from the study team, extracted and crosschecked data, and assessed the risk of bias. RESULTS: Of 1784 articles, 32 articles published from 2003 to 2023 were included. Thirty-one studies were conducted in the United States and one in Australia, with 28 quantitative and four qualitative methodologies. The overall results in terms of breast density awareness, knowledge, communication with healthcare professionals, screening intentions and supplemental screening practice were heterogenous across studies. Barriers to understanding BD notifications and intentions/access to supplemental screening among racial and ethnic minorities included socioeconomic factors, language, health literacy and medical mistrust. CONCLUSIONS: A one-size approach to inform women about their BD may further disadvantage racial and ethnic minority women. BD notification and accompanying information should be tailored and translated to ensure readability and understandability by all women.

Asymmetric distribution of anionic phospholipids in supported lipid bilayers.

Lipid bilayers with a controlled content of anionic lipids are a prerequisite for the quantitative study of hydrophobic-electrostatic interactions of proteins with lipid bilayers. Here, the asymmetric distribution of zwitterionic and anionic lipids in supported lipid bilayers is studied by neutron reflectometry. We prepare POPC/POPS (3:1) unilamellar vesicles in a high-salt-concentration buffer. Initially, no fusion of the vesicles to a SiO(2) surface is observed over hours and days. Once the isotonic buffer is exchanged with hypotonic buffer, vesicle fusion and bilayer formation occur by osmotic shock. Neutron reflectivity on the bilayers formed this way reveals the presence of anionic lipids (d(31)-POPS) in the outer bilayer leaflet only, and no POPS is observed in the leaflet facing the SiO(2) substrate. We argue that this asymmetric distribution of POPS is induced by the electrostatic repulsion of the phosphatidylserines from the negatively charged hydroxy surface groups of the silicon block. Such bilayers with controlled and high contents of anionic lipids in the outer leaflet are versatile platforms for studying anionic lipid protein interactions that are key elements in signal transduction pathways in the cytoplasmic leaflet of eukaryotic cells.

Gap junctions as modulators of adrenal cortical cell proliferation and steroidogenesis.

Gap junctions are membrane specializations that are composed of connexin protein. The assembly of these proteins into channels between cells allows for the intercellular transfer of regulatory molecules. In the adrenal gland, as in most other tissues, intercellular communication provides the potential for regulation of a number of complex interactive cell processes including differentiation, steroidogenesis, migration, and proliferation. This review is concerned with the regulation of gap junctions and cell function in cortical cells of the adrenal gland and in pathological disorders such as adrenal cancer.

D-24851, a novel synthetic microtubule inhibitor, exerts curative antitumoral activity in vivo, shows efficacy toward multidrug-resistant tumor cells, and lacks neurotoxicity.

N-(pyridin-4-yl)-[1-(4-chlorbenzyl)-indol-3-yl]-glyoxyl-amid (D-24851) is a novel synthetic compound that was identified in a cell-based screening assay to discover cytotoxic drugs. D-24851 destabilizes microtubules and blocks cell cycle transition specifically at G2-M phase. The binding site of D-24851 does not overlap with the tubulin binding sites of known microtubule-destabilizing agents like vincristine or colchicine. In vitro, D-24851 has potent cytotoxic activity toward a panel of established human tumor cell lines including SKOV3 ovarian cancer, U87 glioblastoma, and ASPC-1 pancreatic cancer cells. In vivo, oral D-24851 treatment induced complete tumor regressions (cures) in rats bearing Yoshida AH13 sarcomas. Of importance is that the administration of curative doses of D-24851 to the animals revealed no systemic toxicity in terms of body weight loss and neurotoxicity in contrast to the administration of paclitaxel or vincristine. Interestingly, multidrug-resistant cell lines generated by vincristine-driven selection or transfection with the Mr 170,000 P-glycoprotein encoding cDNA were rendered resistant toward paclitaxel, vincristine, or doxorubicin but not towards D-24851 when compared with the parental cells. Because of its synthetic nature, its oral applicability, its potent in vitro and in vivo antitumoral activity, its efficacy against multidrug-resistant tumors, and the lack of neurotoxicity, D-24851 may have significant potential for the treatment of various malignancies.

Reduced levels of histones H1o and H1b, and unaltered content of methylated DNA in rainbow trout hepatocellular carcinoma chromatin.

The levels of histone subtypes and DNA methylation of aflatoxin-induced rainbow trout hepatocellular carcinoma and adult liver nuclei were compared. The hepatocellular carcinoma nuclei were enriched in the ubiquitinated species of histone H2A and depleted in histones H1o and H1b. The 5-methylcytosine content and methylation patterns of the vitellogenin genes and the transcriptionally inactive TPG-3 protamine gene were not altered in the trout hepatocellular carcinoma DNA. Thus, undermethylation of DNA is not a general feature of chemically induced tumors in vivo.

Ammonia sensing for enzymatic urea detection using organic field effect transistors and a semipermeable membrane.

Organic Field Effect Transistors (OFETs) are used to measure ammonia in solution via ammonia diffusion into the OFET channel. An increase in ammonia concentrations results in a decrease in transistor currents. The regeneration of the OFET current after ammonia uptake is slow, which allows us to read out the maximum ammonia dose which was applied. A 100 nm parylene-C layer serves as a semipermeable top gate dielectric. The parylene layer is functionalized with the covalently attached enzyme urease. The enzyme catalyses the hydrolysis of urea to ammonia and carbon dioxide, i.e. urea can be detected via its hydrolysis product ammonia. The sensitivity covers a range of physiological concentrations of urea, which are several mM.

The ubiquitinated histone species are enriched in histone H1-depleted chromatin regions.

Bovine thymus and trout testis chromatin were fractionated into regions which differed in their micrococcal nuclease accessibility and solubility properties, and the distribution of the ubiquitinated histone species among these chromatin regions was elucidated. Ubiquitinated (u) species of histones H2A and H2B were enriched in the nuclease-sensitive, low-ionic-strength, soluble fraction of both chromatins. These results indicate that the presence of ubiquitinated histones may alter nucleosome-nucleosome interactions and destabilize higher-order chromatin structures. Bovine thymus chromatin was separated into aggregation-resistant, salt-soluble and aggregation-prone, salt-insoluble chromatin fractions. The aggregation-resistant chromatin fraction depleted in H1 histones was enriched in uH2A and uH2B, with uH2B showing the greater enrichment. The chromatin fragments were also stripped and reconstituted with the H1 histones prior to fractionation. The results were the same as above: uH2A and uH2B were preferentially localized in the aggregation-resistant. H1-depleted chromatin fraction, suggesting that chromatin regions enriched in ubiquitinated histone species have a reduced affinity for the H1 histones. Thus, ubiquitinated histone species may be one of the contributing factors in the differential assembly of various parts of the genome.

The protamine gene chromatin in developing trout testis exists in an altered state.

Micrococcal nuclease was used to probe the nucleosomal organization of the rainbow trout germ-line-specific protamine multi-gene family in testis and erythrocytes. In erythrocyte chromatin, the repressed protamine genes show a distinct nucleosomal repeat pattern. However, in early-stage testis chromatin, where the protamine genes are expressed, they lack a distinct nucleosomal repeat pattern, indicating that the disrupted chromatin structure is related to their transcriptional activity. Micrococcal nuclease-digested testis and erythrocyte chromatin was separated into soluble and insoluble fractions. Transcriptionally active/competent genes of testis that had been labeled by nuclear nick-translation were enriched in the low-salt eluted, micrococcal nuclease-sensitive chromatin fraction. This fraction was not enriched in protamine DNA sequences. In testis, but not erythrocytes, protamine DNA sequences were slightly enriched in chromatin that fractionated with insoluble nuclear material, suggesting that transcriptionally active protamine gene chromatin has an insoluble character. Since the different protamine genes may not be simultaneously expressed, our results show the distribution of both transcriptionally active and inactive protamine genes. However, our observations indicate that the active germ-line-specific protamine gene chromatin shares several, but not all, of the features associated with other active tissue-specific genes.

Thermal conductivity and bulk viscosity in quartic oscillator chains.

We propose a relation which predicts the low-frequency thermal conductivity of a one-dimensional (1D) system from the thermal conductivity and bulk viscosity at higher frequency. Our theory is based on the assumption that "ballistic" transport by sound waves dominates the heat transport. For a system with equal heat capacities (c(p) = c(v)) this relation is particularly simple. We test the prediction by simulating a chain of particles with quartic interparticle potentials under zero pressure conditions. As the frequency omega --> 0 the theory predicts that the energy current power spectrum diverges as omega(-1/2), not seen in previous simulations. Because we simulate very long chains to long times we do observe the crossover into this regime. The bulk viscosity of a 1D chain has been determined via simulation. It is found to be finite for our system, in contrast to the thermal conductivity which is infinite.

Evidence of convective constraint release during hole growth in freely standing polystyrene films at low temperatures.

Hole growth measurements were performed using optical microscopy on freely standing polystyrene films at temperatures that were slightly larger than the bulk value of the glass transition temperature T(bulk)g. For the measured range of temperatures, we have observed a transition from linear growth of the hole radius R during the early stages to exponential growth of R at later times. We have characterized this transition as a function of molecular weight 120 x 10(3) < Mw <2240 x 10(3) , film thickness 61 nm

Tissue-specific expression and thyroid hormone regulation of the endogenous placental growth hormone variant and chorionic somatomammotropin genes in a human choriocarcinoma cell line.

Human (h) placenta-derived choriocarcinoma cell lines (BeWo, JAR, and JEG-3) were examined for expression of pituitary GH (hGH-N) as well as placental GH variant (hGH-V) and chorionic somatomammotropin (hCS, encoded by the hCS-A or hCS-B gene). RNA was isolated and assessed using hGH-N complementary DNA since hGH and hCS genes share more than 90% sequences similarity. The relative expression is BeWo greater than JAR greater than JEG-3. In BeWo cells expression of placental hCS-A, hCS-B, and hGH-V genes, but not pituitary hGH-N, is observed using polyadenylated RNA and oligonucleotide probes specific for the different family members. The absence of hGH-N expression in BeWo cells is not due to deletion or gross rearrangement of the gene. No difference was seen between the hGH/hCS genes in genomic DNA from these cells and the DNA from placenta and pituitary when analyzed by restriction digestion and blotting. Treatment of BeWo cells with 10 nM T3 results in a 6-fold increase in messenger RNA from placental members of the hGH gene family. Levels of hCS-A, hCS-B, and hGH-V transcripts are all elevated. Cellular and secreted proteins from BeWo cells were analyzed by Western blotting, and a band of about 22 kilodaltons was detected using a polyclonal antibody which cross-reacts with hGH-V and hCS. The level of 22 kilodalton band in samples of cellular as well as released protein was increased by T3 treatment. BeWo cells provide a model system for studying hGH-V and hCS regulation as well as tissue-specific expression.

The human placental growth hormone variant is mitogenic for rat lymphoma Nb2 cells.

Although there is evidence that human (h) placental GH variant (hGH-V) possesses a growth-promoting function, lactogenic activity by the hormone has not been demonstrated. Rat anterior pituitary tumor (GC) cells stably transfected with the hGH-V gene (GC [hGH-V] cells) synthesize and secrete hGH-V. This hormone shares considerable structural similarity with pituitary growth hormone (hGH-N) and chorionic somatomammotropin (hCS) at the nucleotide (greater than 90%) and amino acid (greater than 80%) levels. As expected, both hGH-N and hCS antibodies detect hGH-V by immunoblotting. However, hGH-V, but not hGH-N or hCS, cross-reacts with human or rat pituitary prolactin (PRL) antibodies. These data indicate that structural features shared by hGH-V and pituitary PRL are not present in hGH-N or hCS. Comparison of amino acid sequences implicates two regions that may account for a common epitope between hGH-V and hPRL, and structural difference from hGH-N and hCS. The possible lactogenic activity by hGH-V was assessed in a rat lymphoma Nb2 cell bioassay. Conditioned medium from GC[hGH-V] cells permitted growth of lactogen-dependent Nb2 lymphoma cells in culture. This activity was blocked by antibodies raised to rat PRL but not hPRL or hGH-N. Comparison of the hGH-V amino acid sequence with those from 14 other lactogenic hormones, including hPRL, hCS and hGH-N, reveals 6 conserved amino acids. These data indicate a lactogenic as well as growth-promoting function for the secreted hGH-V protein in vivo.

Allelic association of a dopamine transporter gene polymorphism in alcohol dependence with withdrawal seizures or delirium.

Hereditary factors confer susceptibility to alcohol dependence. Alcohol mediates its reinforcing effects by enhancing dopamine activity in the mesolimbic dopamine system. The role of the dopamine transporter in terminating dopaminergic activity in synaptic neurotransmission suggests that variants of the dopamine transporter gene (DAT1) might contribute to individual differences in vulnerability to addictive behavior. Our population-based association study investigated whether variants of DAT1 confer susceptibility to alcohol dependence in 293 alcoholics and clinically more homogeneous subgroups formed by: positive family history, early age-at-onset, delirium, withdrawal seizures, antisocial tendencies, type 1 and 2 alcoholics. Analyzing a VNTR polymorphism in the 3' untranslated region of DAT1, we found a significantly increased prevalence of the nine-repeat allele in 93 alcoholics displaying withdrawal seizures or delirium, compared with 93 ethnically matched nonalcoholic controls (p = 0.003; OR = 2.44; 95% confidence interval: 1.35-4.43). Our data provide evidence that a major genetic determinant of DAT1 influences vulnerability to severe alcohol withdrawal symptoms.

Evaluation of physical dependence liability of l-deprenyl (selegiline) in animals.

l-Deprenyl is a useful drug that has been successful in the clinical treatment of parkinsonism. However, l-deprenyl is a phenylalkylamine derivative that undergoes metabolic transformation to l-methamphetamine and l-amphetamine. Therefore, the question arises whether l-deprenyl possesses amphetamine-like abuse liability. This article reviews a series of different preclinical studies in rats that used experimental procedures to provide preclinical information predictive of human abuse liability. In one series we investigated whether repeated administration of l-deprenyl to rats resulted in observable signs of physical dependence. In a second series of studies, the effects of l-deprenyl on the cortical electrical activity of freely moving rats were investigated. Finally, the influence of l-deprenyl on behavior of the animals was studied. In all studies, different stereospecific configurations of amphetamine and deprenyl were compared. During and after 6 weeks of oral administration of l-deprenyl, no signs of physical dependence were observed in rats after withdrawal of the drug. In contrast, with d-deprenyl, d-amphetamine, and racemic d,l-amphetamine, signs indicative of physical dependence were observed after withdrawal of the drug. For example, the body weight of the rats was increased. In addition, changes in electroencephalograms and behavior of rats induced by l-deprenyl and l-amphetamine were different from those produced by the d-enantiomers. Thus preclinical results confirm the clinical experience that therapeutically relevant doses of l-deprenyl are without physical dependence liability.

Herpesvirus saimiri transformed T cells and peripheral blood mononuclear cells restimulate identical antigen-specific human T cell clones.

Panels of human antigen-specific T cell clones (TCC) have been established by limiting dilution using Herpesvirus saimiri (HVS) subtype C transformed T cells as antigen presenting cells (APC). They showed antigen-specific proliferation when peripheral blood mononuclear cells (PBMC), HVS-transformed T cells and Epstein Barr Virus transformed lymphoblastoid B cell lines (EBV-LCL) were used as APC. All T cell clones were CD4+ and HLA class II restricted. For a detailed analysis, two panels of T cell clones specific for an epitope located in the N-terminus of the Merozoite Surface Protein 1 (MSP-1) of Plasmodium falciparum were established from the same founder T cell line using either PBMC or HVS-transformed T cells as APC. TCR analysis of the two panels of TCC demonstrated that the same founder cells could be propagated in both culture systems. Furthermore, no difference in the cytokine expression pattern or antigen processing and co-stimulatory requirements was observed between TCC established on PBMC or HVS-transformed T cells. Based on the finding that HVS-transformed T cells can replace PBMC as APC for isolation and propagation of antigen-specific TCC, a protocol was developed and successfully executed, which allows to establish and maintain vaccine-specific T cell clones from 20 ml of blood. This method might be particularly significant in clinical trials of immune intervention strategies.

Arrest of Trypanosoma brucei rhodesiense and T. brucei brucei in the S-phase of the cell cycle by (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine ((S)-HPMPA).

African trypanosomes are incapable of purine de novo synthesis. They use salvage pathways to meet their purine requirements. Therefore, purine analogues appear as potential candidates to interfere in trypanosome metabolism. The acyclic adenosine analogue (S)-9-(-3-hydroxy-2-phosphonylmethoxypropyl)adenine ((S)-HPMPA) expressed antitrypanosomal activity in vitro and vivo. When exposed to 20 microM (S)-HPMPA, trypanosomes were arrested in the S-phase of the cell cycle and were unable to enter G2-phase. Thymidine uptake and incorporation was inhibited almost completely. Only nuclear DNA replication was inhibited, while mitochondrial DNA replication and kinetoplast division was not inhibited. The antitrypanosomal effect was reversible when cells were exposed for 12 h. As a control, aphidicolin arrested trypanosomes in the G1-phase of the cell cycle at a concentration of 30 microM. At 20 microM (S)-HPMPA, glycolysis was not effected, while leucine and adenine uptake were reduced with prolonged exposure.