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An untitled poem by Sharon Hammer Baker is presented. First Line: a gull keens; Last Line: another lure cast.

Abstract: Sulfotransferases (SULTs) catalyzed sulfation is important in the regulation of biological activities of hormones and neurotransmitters, the metabolism of drugs, and the detoxification of xenobiotic toxicants. Sulfation also leads to the bioactivation of procarcinogens. Human dehydroepiandrosterone sulfotransferase (hSULT2A1) is a major SULT catalyzing the sulfation of hydroxysteroids and xenobiotic alcohols. Our previous studies had shown that the anti-folate drug methotrexate (MTX) can up-regulate several major isoforms of human SULTs. To determine the mechanisms controlling the regulation of hSULT2A1, the 5′-flanking region of hSULT2A1 was constructed into the pGL3-Basic luciferase reporter vector. The transcriptional regulation mechanism of hSULT2A1 promoter was studied using Caco-2 cell line based on the reporter gene assay. Nuclear receptor co-transfection results indicated that human constitutive androstane receptor (hCAR) and human retinoid X receptor α (hRXRα) were involved in the transcriptional regulation of hSULT2A1. RNA interference experiments further proved the role of hCAR in hSULT2A1 regulation. Progressive promoter deletion, DNA sequence alignment, and site directed promoter mutation results suggested that an imperfect inverted repeat DNA motif, IR2 (−186AGCTCAGATGACCC−173), within the hSULT2A1 promoter region mediated the hSULT2A1 induction by MTX. Furthermore, electrophoretic mobility shift assay and super shift assay were employed to characterize the interactions of hCAR and hRXRα with the IR2 element. In summary, we identified an IR2 DNA cis-element located at −186/−173 of hSULT2A1 promoter region; the IR2 element mediates the MTX induction of hSULT2A1 through interacting with hCAR and hRXRα. [Copyright &y& Elsevier]

Sulfotransferase (SULT) catalyzed sulfation is responsible for hormone regulation and xenobiotic detoxification. Induction of SULTs by various hormones has been reported. Stress regulation of SULTs has not been reported, however. Here we report that rat liver SULTs can be regulated by physical stress (forced running, EX) and chemical stress (the organophosphorus pesticide parathion, PS). Both EX and PS increased rat liver phenol-sulfating SULT1A1 and hydroxysteroid-sulfating SULT2A1 activities. The increase in SULT1A1 activity did not correlate with protein (Western blot) or mRNA (RT-PCR) results but correlated well with increased non-protein soluble thiols. This suggests a possible Cys modification mechanism for stress regulation of SULT1A1. In vitro studies on GSH/GSSG effects on SULT1A1 activity support this conclusion. In contrast, SULT2A1 activity following physical or chemical stress treatments correlated well with protein and mRNA levels. This suggests a stress regulation mechanism of SULT2A1 at the gene transcription level, possibly occurring via hormones. [Copyright &y& Elsevier]

The research presents tests of traditional and augmented versions of Fishbein and Ajzen's Theory of Reasoned Action (TRA), applied to condom use among adult clients of a sexually transmitted disease clinic. In a longitudinal survey, predictor variables suggested by Ajzen and Fishbein (1980), plus gender and condom use self-efficacy, were measured at Time 1. Condom use Time 2, 3 months later, was regressed onto these variables. The traditional TRA worked well to predict condom use intentions and behavior. Support was also found for inclusion of gender and self-efficacy in the prediction of intention to use condoms, but not behavior. Implications for interventions to increase condom use among those at high risk for AIDS and other STDs are discussed. [ABSTRACT FROM AUTHOR]

Thiazolidinediones (TZDs) are insulin-sensitising drugs that are ligands for the nuclear receptor PPARγ. They have been shown to inhibit PMA-stimulated secretion of TNFα from human monocytes, although only at concentrations well in excess of circulating levels observed during TZD therapy, suggesting a mechanism of action independent of PPARγ activation. Here we show that insulin-sensitising concentrations of the TZD rosiglitazone partially inhibit serum- or LPS- (but not PMA-) stimulated TNFα secretion from primary human monocytes, with an IC50 of around 50 nM. We also show that the observed effects are independent of PPARγ-mediated regulation of the lipid phosphatase PTEN. Reversed stimulus specificity, IC50 in the insulin-sensitising range, and the fact that partial inhibition of TNFα secretion is also observed with a structurally unrelated PPARγ agonist, GW7845, demonstrate a mechanism of action distinct from that observed with higher TZD concentrations. These findings thus represent the first report of a PPARγ-dependent and therapeutically relevant anti-inflammatory action of TZDs in isolated human monocytes. [Copyright &y& Elsevier]

Elevated troponin is increasingly recognized as a marker of cardiac injury and poor outcomes in diverse disease states. It was hypothesized that patients with infective endocarditis (IE) and elevated cardiac troponin would have more extensive IE and worse clinical outcomes. Patients were enrolled as part of the International Collaboration on Endocarditis (ICE) prospective cohort study; analysis of these patients was done retrospectively. Data from 83 consecutively enrolled patients from a single center were evaluated. Cardiac troponin I (cTnI) was drawn for clinical indications and before any cardiac surgery in 51 of the 83 patients. Outcomes evaluated were hospital mortality, annular or myocardial abscess on the basis of echocardiography or surgery, and central nervous system events. Of 51 patients with cTnI drawn, 33 (65%) had elevated cTnI ≥0.1 mg/dl. There were no differences in age, gender, prosthetic valve IE, Staphylococcus aureus IE, or history of coronary artery disease, congestive heart failure, or diabetes mellitus between patients with and without cTnI elevations. Patients with elevated cTnI were less likely to have isolated right-sided IE and more likely to have left ventricular systolic dysfunction or renal dysfunction (p <0.05 for each). In conclusion, elevated cTnI was associated with the composite of death, abscess, and central nervous system events (p <0.001). [Copyright &y& Elsevier]

Background: Children with cleft palate are at high risk of both conductive hearing loss and cleft speech characteristics (CSCs) yet there is limited research to understand whether hearing loss impacts speech development in this population by contributing to the development of CSCs., Aims: This study used data from a large national cohort study in the UK (The Cleft Collective) to explore the relationship between those with a history of diagnosed hearing loss and presence of CSCs in children with cleft palate (+/- cleft lip) aged between 18 and 24 months., Method: Speech and Language Therapists (SLTs) provided uniformed information from assessment for 123 participants who had been recruited to the Cleft Collective study. History of diagnosed hearing loss, intervention for hearing loss, and presence of CSCs were reported. A consonant inventory for each participant was completed. Statistical analysis of relationships between hearing loss and CSCs and analysis of consonant inventories was undertaken to provide information related to speech acquisition and its relationship with hearing., Results: There was a statistically significant relationship between history of diagnosed hearing loss and presence of CSCs (p < 0.05). Analysis of the consonant inventories highlighted that children with diagnosed hearing loss used fewer oral consonants compared to those with normal hearing (p < 0.05) CONCLUSION: This study provides some evidence that a conductive hearing loss can affect speech in children with cleft palate resulting in CSCs developing. Therefore, children with cleft palate should be closely monitored by audiology from birth to ensure that hearing is optimised for speech and language development. SLT services should also closely monitor the speech development of those children where a hearing loss has been identified, so that early intervention can be provided if appropriate. Continued data collection, with a large sample of children, will provide additional evidence regarding how this hearing loss is best managed. It will also allow increased knowledge of the long term impact of conductive hearing loss on speech development in children with cleft palate., (Copyright © 2021. Published by Elsevier B.V.)

For decades , research has focused on American Sign Language/English bilingual education for d/Deaf and hard of hearing students whose families used English or ASL. However, a growing population of d/Dhh children come from households where languages other than English (e.g., Spanish, Chinese, Vietnamese) are used. In a longitudinal case study, the authors document the K-12 educational pathway of a deaf Latina student. Anecdotal records, semistructured interviews, assessment data, and document reviews of the participant's school and clinical records are used to develop the case study. The findings provide the basis for recommendations for future research and for critical factors to consider to improve the education of d/Dhh Multilingual Learners (DMLs). These include ensuring appropriate educational placements, addressing early communication and language needs, determining effective instructional techniques and assessments, strengthening the L1 to support L2 learning, and providing students with opportunities to learn their heritage language.

Background: Obesity is a prominent problem in the United States and in North Carolina. One way of combating it is with community-engaged interventions that foster collaboration between health-oriented organizations and community residents., Purpose: Our purpose was to assemble a multifaceted group in Durham, North Carolina, to identify factors affecting obesity-related lifestyle behaviors; assess policies, resources, and the population's perception of the problem of obesity; and develop plans to improve health outcomes related to obesity., Methods: A team consisting of more than 2 dozen partners was assembled to form Achieving Health for a Lifetime (AHL) in order to study and address obesity in the community, initially focusing on elementary school-age children. The team developed a resource guide by collecting information by telephone interviews of provider organizations; geospatial resource maps were created using high-resolution geographic information systems, Duke's Data Support Repository, and county and city records; and focus groups were conducted using the nominal group technique., Results: The AHL team, in collaboration with 2 other teams focused on diabetes and cardiovascular disease, identified 32 resources for diabetes, 20 for obesity, and 13 for cardiovascular disease. Using Geographic Information Systems (GIS), the team identified an area of Durham that had only 1 supermarket, but 34 fast-food restaurants and 84 convenience stores., Limitations: The focus on particular neighborhoods means that the information obtained might not pertain to all neighborhoods., Conclusion: The AHL team was able to assemble a large community partnership in Durham that will allow the members of the community to continue to work toward making residents healthier. Communities facing similar challenges can learn from this experience.

OBJECTIVE: Lack of support for breastfeeding mothers has been consistently identified in the literature as a barrier for breastfeeding across racial and ethnic groups. Using a community-based participatory approach, academic and community-based partners conducted an iterative process to assess barriers, facilitators and potential mediating interventions for breastfeeding in the African-American community in Durham, North Carolina. METHODS: Eight focus groups were conducted with African-American mothers, fathers and grandmothers. Researchers transcribed and coded each focus group and analyzed using Atlas ti. 5.2. Patterns and themes that emerged informed the development of community stakeholder interviews; 41 interviews were conducted with community representatives. These findings informed the development of a support group pilot intervention. The pilot support groups were evaluated for increase in knowledge of attendees. RESULTS: Focus group and community interviews indicate that African Americans may disproportionately experience inadequate support for breastfeeding. This lack of support was reported in the home, the workplace, among peers, and from healthcare providers. The pilot support groups resulted in increased knowledge of breastfeeding among group participants OR=3.6 (95% CI: 2.5, 5.2). CONCLUSIONS: The findings from this research underscore the importance of a multi-level approach to breastfeeding support for African American women to address breastfeeding disparities.

A study was conducted to identify the norms, values, and perceptions of urban immigrant Mexican American (MA) parents of school children relative to physical activity, healthy eating, and child risk factors for type 2 diabetes. Investigators facilitated five focus groups in an urban elementary school setting and analyzed data using qualitative analysis techniques. Methods for participant recruitment, conduct of focus groups, and qualitative data analysis are detailed. Results of analysis are presented. The relationship between parent focus group discussion and the conceptual framework guiding the study are depicted. Implications for practice and research are discussed.

While the proteome defines the expressed gene products, the metabolome results from reactions controlled by such gene products. Plasma represents an accessible "window" to the metabolome both in regard of availability and content. The wide range of the plasma metabolome, in terms of molecular diversity and abundance, makes its comprehensive analysis challenging. Here we demonstrate an analytical method designed to target one region of the metabolome, that is, oxysterols. Since the discovery of their biological activity as ligands to nuclear receptors there has been a reawakening of interest in oxysterols and their analysis. In addition, the oxysterols, 24S- and 27-hydroxycholesterol, are currently under investigation as potential biomarkers associated with neurodegenerative disorders such as Alzheimer's disease and multiple sclerosis; widespread analysis of these lipids in clinical studies will require the development of robust, sensitive and rapid analytical techniques. In this communication we present results of an investigation of the oxysterols content of human plasma using a newly developed high-performance liquid chromatography-mass spectrometry (HPLC-MS) method incorporating charge-tagging and high-resolution MS. The method has allowed the identification in plasma of monohydroxylated cholesterol molecules, 7alpha-, 24S-, and 27-hydroxycholesterol; the cholestenetriol 7alpha,27-dihydroxycholesterol; and 3beta-hydroxycholest-5-en-27-oic acid and its metabolite 3beta,7alpha-dihydroxycholest-5-en-27-oic acid. The methodology described is also applicable for the analysis of other sterols in plasma, that is, cholesterol, 7-dehydrocholesterol, and desmosterol, as well as cholesterol 5,6- seco-sterols and steroid hormones. Although involving derivatization, sample preparation is straightforward and chromatographic analysis rapid (17 min), while the MS method offers high sensitivity (ng/mL of sterol in plasma, or pg on-column) and specificity. The methodology is suitable for targeted metabolomic analysis of sterols, oxysterols, and steroid hormones opening a "window" to view this region of the metabolome.

The Group IVA cytosolic phospholipase A2 (GIVA cPLA2) is a key provider of substrates for the production of eicosanoids and platelet-activating factor. We explored the structure-activity relationship of 2-oxoamide-based compounds and GIVA cPLA2 inhibition. The most potent inhibitors are derived from delta- and gamma-amino acid-based 2-oxoamides. The optimal side-chain moiety is a short nonpolar aliphatic chain. All of the newly developed 2-oxoamides as well as those previously described have now been tested with the human Group V secreted PLA2 (GV sPLA2) and the human Group VIA calcium-independent PLA2 (GVIA iPLA2). Only one 2-oxoamide compound had appreciable inhibition of GV sPLA2, and none of the potent GIVA cPLA2 inhibitors inhibited either GV sPLA2 or GVIA iPLA2. Two of these specific GIVA cPLA2 inhibitors were also found to have potent therapeutic effects in animal models of pain and inflammation at dosages well below the control nonsteroidal anti-inflammatory drugs.

Three 16-month sexual risk-taking trajectories were identified in 287 women in an STD/HIV intervention study. The Risk Eliminator group reported no sex risk following intervention while the Risk Reducer group reported continuous drops over time. The High Risk group reported higher initial risk than the other two and no subsequent changes. The trajectory groups showed no between- or within-group effects of intervention exposure. Trajectory groups were compared on baseline characteristics. No differences were seen in demographics or STD/HIV knowledge. Compared to one or both of the other groups, the High Risk women reported more lifetime partners, recent paying partners, adult rape, and recent substance use. Their steady partners were more likely to be abusive, intoxicated during sex (as were the women themselves), and believed to be non-monogamous. The Risk Eliminator group differed from the other two by being less likely to report a history of childhood sexual abuse.

Background: The male genital tract is a complex collection of anatomically and biochemically distinct compartments that contribute to the ejaculate. Understanding the pharmacokinetics in these compartments should inform rational therapeutics involving these glands., Methods: Nineteen men were administered a single dose of 600 mg chloroquine (base) and 975 mg aspirin before providing a semen sample by masturbation with fractionation into a 5-compartment collection device. Fractions were assayed for fructose (unique seminal vesicle marker), prostate-specific antigen (unique prostate marker), salicylate, and chloroquine. Seminal vesicle and prostate concentrations of salicylate and chloroquine were estimated via a novel analytic method involving a multilevel latent-variable model implemented by use of Bayesian methods., Results: The geometric mean chloroquine semen/blood ratio was 4.02 (95% confidence interval [CI], 2.36-6.86); for salicylate, the primary metabolite of aspirin, the semen/blood ratio was 0.10 (95% CI, 0.08-0.14). The estimated mean prostate/seminal vesicle ratio for salicylate, 0.38 (95% CI by Bayesian methods, 0.12-0.73), was consistent with our hypothesis that salicylate would achieve higher concentrations in the seminal vesicle than in the prostate. Chloroquine, however, did not demonstrate a statistically significant seminal vesicle/prostate difference (4.41; 95% CI by Bayesian methods, 0.14-30.52)., Conclusions: We successfully demonstrated the quantitative, noninvasive estimation of drug concentrations in the prostate gland fluid distinct from the seminal vesicle fluid using our optimized method of split-ejaculate collection and a novel mixed-effects model with Bayesian estimation. Our methods can be applied to gland-specific quantitation of drugs and other substances of interest, thus enabling pharmacokinetic, pharmacodynamic, and pathophysiologic studies to inform rational therapeutics within different glands of the male genital tract.

A method for the quantitative assay of mammalian cell micropermeabilization is described. The method is based on the permeabilization-induced loss of endogenous glycolytic cofactors and consequent discontinuation of cellular lactate production. Advantages of the method include sensitivity and precision similar to that of micropermeabilization assays based on the release of 86Rb+ from preloaded cells, avoidance of radioactivity, and simplicity of the measurements and equipment required.

Evidence for the NADH-modulated formation of a complex between alpha-glycerol-3-phosphate dehydrogenase and l-lactate dehydrogenase was reported [Yong, H., Thomas, G. A., and Peticolas, W. L. (1993) Biochemistry 32, 11124-11131]. This NADH-modulated association suggested a mechanism of potentially great importance to enzyme modulation and the controversial phenomena of direct NADH channeling. In the present paper, we reproduce with additional controls the experiments described by Yong et al. ((1993) Biochemistry 32, 11124-11131). Our results conclusively demonstrate the absence of detectable association between alpha-glycol-3-phosphate dehydrogenase and l-lactate dehydrogenase.

Context: Most research on heterosexual transmission of HIV and other sexually transmitted diseases (STDs) has focused on women. However, heterosexual transmission of STDs cannot be prevented without a better understanding of men's, as well as women's, sexual beliefs and behaviors., Methods: Heterosexually active men's beliefs about four methods of STD prevention--abstinence, mutual monogamy, use of male condoms and use of female condoms--were elicited through open-ended interviews. A survey based on these responses was administered to a random sample of 486 heterosexually active men, and scores were calculated to examine their beliefs about each behavior. Additional analyses explored how these beliefs were related to men's characteristics and to their actual behavior., Results: The men held both positive and negative beliefs about the outcomes of using each method and thought that their partners, close friends, health care providers, family members and, to some extent, friends at church had opinions about whether they should use each method. Multiple regression analyses showed that the men's beliefs were related to their marital status and, to some extent, their race or ethnicity and education. Beliefs about the outcomes of practicing abstinence, practicing mutual monogamy and using male condoms with steady partners were significantly related to these behaviors; beliefs about whether they had support for practicing monogamy or using male condoms with steady partners were significant predictors of doing so., Conclusions: Encouraging safer-sex practices among heterosexually active men will require addressing their beliefs and perceived norms about alternative methods of preventing STDs.

Thiazolidinediones (TZDs) are insulin-sensitising drugs that are ligands for the nuclear receptor PPAR gamma. They have been shown to inhibit PMA-stimulated secretion of TNFalpha from human monocytes, although only at concentrations well in excess of circulating levels observed during TZD therapy, suggesting a mechanism of action independent of PPAR gamma activation. Here we show that insulin-sensitising concentrations of the TZD rosiglitazone partially inhibit serum- or LPS- (but not PMA-) stimulated TNF alpha secretion from primary human monocytes, with an IC(50) of around 50nM. We also show that the observed effects are independent of PPAR gamma-mediated regulation of the lipid phosphatase PTEN. Reversed stimulus specificity, IC(50) in the insulin-sensitising range, and the fact that partial inhibition of TNF alpha secretion is also observed with a structurally unrelated PPAR gamma agonist, GW7845, demonstrate a mechanism of action distinct from that observed with higher TZD concentrations. These findings thus represent the first report of a PPAR gamma-dependent and therapeutically relevant anti-inflammatory action of TZDs in isolated human monocytes.

Loss of epithelial cell polarity, which can arise following disruption of tight junctions (TJs), is a precursor to the care-fully orchestrated removal of moribund cells from epithelia in apoptosis. Ordinarily, this cycle of events has minimally disruptive effects on the function of the epithelial barrier, but some agents have been identified that induce apoptosis and promote epithelial leakiness. The allergen Der p 1 is a cysteine peptidase that cleaves TJ adhesion proteins and induces apoptosis in epithelial cells. This suggests the possibility that, at least for some inducers of apoptosis, these events might be causally linked. We report here that Der p 1 induces epithelial apoptosis before outright cell detachment and that apoptosis occurs within the same time span as increased paracellular permeability in polarized epithelial monolayers. Whilst TJ-deficient BEAS-2B cells were resistant to Der p 1-induced apoptosis, the cell line 1HAEo-, which was also TJ deficient, was sensitive to Der p 1, providing evidence against TJ proteolysis as a cause of apoptosis. To provide direct evidence, we propagated cells that normally express TJs in low calcium medium that prevented intercellular junction assembly. These cells retained full susceptibility to Der p 1, indicating that Der p 1-induced apoptosis is independent from TJ proteolysis.