Seeking Inspiration: Examining the Validity and Reliability of a New Smartphone Respiratory Therapy Exergame App.

BACKGROUND: Clinically valid and reliable simulated inspiratory sounds were required for the development and evaluation of a new therapeutic respiratory exergame application (i.e., QUT Inspire). This smartphone application virtualises incentive spirometry, a longstanding respiratory therapy technique. OBJECTIVES: Inspiratory flows were simulated using a 3 litre calibration syringe and validated using clinical reference devices. Syringe flow nozzles of decreasing diameter were applied to model the influence of mouth shape on audible sound levels generated. METHODS: A library of calibrated audio inspiratory sounds was created to determine the reliability and range of inspiratory sound detection at increasing distances separating the sound source and smartphones running the app. RESULTS: Simulated inspiratory sounds were reliably detected by the new application at higher air inflows (high, medium), using smaller mouth diameters (<25 mm) and where smartphones were held proximal (≤5 cm) to the mouth (or at distances up to 50 cm for higher airflows). Performance was comparable for popular smartphone types and using different phone orientations (i.e., held horizontally, at 45° or 90°). CONCLUSIONS: These observations inform future application refinements, including prompts to reduce mouth diameter, increase inspiratory flow and maintain proximity to the phone to optimise sound detection. This library of calibrated inspiratory sounds offers reproducible non-human reference data suitable for development, evaluation and regression testing of a therapeutic respiratory exergame application for smartphones.

Protective hinge in insulin opens to enable its receptor engagement.

Insulin provides a classical model of a globular protein, yet how the hormone changes conformation to engage its receptor has long been enigmatic. Interest has focused on the C-terminal B-chain segment, critical for protective self-assembly in ß cells and receptor binding at target tissues. Insight may be obtained from truncated "microreceptors" that reconstitute the primary hormone-binding site (α-subunit domains L1 and αCT). We demonstrate that, on microreceptor binding, this segment undergoes concerted hinge-like rotation at its B20-B23 ß-turn, coupling reorientation of Phe(B24) to a 60° rotation of the B25-B28 ß-strand away from the hormone core to lie antiparallel to the receptor's L1-ß2 sheet. Opening of this hinge enables conserved nonpolar side chains (Ile(A2), Val(A3), Val(B12), Phe(B24), and Phe(B25)) to engage the receptor. Restraining the hinge by nonstandard mutagenesis preserves native folding but blocks receptor binding, whereas its engineered opening maintains activity at the price of protein instability and nonnative aggregation. Our findings rationalize properties of clinical mutations in the insulin family and provide a previously unidentified foundation for designing therapeutic analogs. We envisage that a switch between free and receptor-bound conformations of insulin evolved as a solution to conflicting structural determinants of biosynthesis and function.

The MAFB transcription factor impacts islet α-cell function in rodents and represents a unique signature of primate islet ß-cells.

Analysis of MafB(-/-) mice has suggested that the MAFB transcription factor was essential to islet α- and ß-cell formation during development, although the postnatal physiological impact could not be studied here because these mutants died due to problems in neural development. Pancreas-wide mutant mice were generated to compare the postnatal significance of MafB (MafB(Δpanc)) and MafA/B (MafAB(Δpanc)) with deficiencies associated with the related ß-cell-enriched MafA mutant (MafA(Δpanc)). Insulin(+) cell production and ß-cell activity were merely delayed in MafB(Δpanc) islets until MafA was comprehensively expressed in this cell population. We propose that MafA compensates for the absence of MafB in MafB(Δpanc) mice, which is supported by the death of MafAB(Δpanc) mice soon after birth from hyperglycemia. However, glucose-induced glucagon secretion was compromised in adult MafB(Δpanc) islet α-cells. Based upon these results, we conclude that MafB is only essential to islet α-cell activity and not ß-cell. Interestingly, a notable difference between mice and humans is that MAFB is coexpressed with MAFA in adult human islet ß-cells. Here, we show that nonhuman primate (NHP) islet α- and ß-cells also produce MAFB, implying that MAFB represents a unique signature and likely important regulator of the primate islet ß-cell.

Hemodialysis Catheter-Associated Right Atrial Thrombus Diagnosed via Point of Care Transesophageal Echocardiogram.

Catheter-associated right atrial thrombus (CRAT) is a potential complication of central venous catheter placement and is associated with an increase in morbidity and mortality. The precise incidence of CRAT is unknown, and there is a lack of clear screening and management guidelines for this condition. Additionally, the diagnosis is often missed when using transthoracic echocardiography (TTE) alone. Here, we present a case of a 64-year-old female admitted to the medical intensive care unit with multiorgan dysfunction who was diagnosed with hemodialysis catheter-associated right atrial thrombus (HDCRAT) via intensivist-performed point of care transesophageal echocardiography (TEE) after an initial TTE was negative. This patient was successfully treated with systemic anticoagulation, local thrombolysis, and delayed removal of the temporary hemodialysis catheter. Our experience serves to highlight the improved visualization of the right atrium and the diagnostic superiority of HDCRAT with TEE. We suspect that with greater utilization of TEE among intensivists, CRAT and HDCRAT will have increased recognition. It is imperative that intensivists are aware of this complication and various management strategies. Still, more studies are needed to establish clear management guidelines for CRAT and the associated complications.

Barriers Faced by Australian and New Zealand Women When Sharing Experiences of Family Violence with Primary Healthcare Providers: A Scoping Review.

Despite the Australian Government's attempts to reduce domestic violence (DV) incidences, impediments within the social and health systems and current interventions designed to identify DV victims may be contributing to female victims' reluctance to disclose DV experiences to their primary healthcare providers. This scoping review aimed to provide the state of evidence regarding reluctance to disclose DV incidents, symptoms and comorbidities that patients present to healthcare providers, current detection systems and interventions in clinical settings, and recommendations to generate more effective responses to DV. Findings revealed that female victims are reluctant to disclose DV because they do not trust or believe that general practitioners can help them to solve their issues, and they do not acknowledge that they are in an abusive relationship, and are unaware that they are in one, or have been victims of DV. The most common symptoms and comorbidities victims present with are sleep difficulties, substance use and anxiety. Not all GPs are equipped with knowledge about comorbidities signalling cases of DV. These DV screening programs are the most prominent intervention types within Australian primary health services and are currently not sufficiently nuanced nor sensitive to screen with accuracy. Finally, this scoping review provides formative evidence that in order for more accurate and reliable data regarding disclosure in healthcare settings to be collected, gender power imbalances in the health workforce should be redressed, and advocacy of gender equality and the change of social structures in both Australia and New Zealand remain the focus for reducing DV in these countries.

Women's Empowerment Through Access to Safe Transport: The Impact of Sexual and Nonsexual Victimization on Female Commuters in Bangladesh and Cambodia.

An examination of women's experience on public transport in Bangladesh and Cambodia found that victimization does reduce perceived safety or transport use. In a cultural context where women are socialized to fear and avoid public spaces, experiencing victimization may confirm rather than change previous beliefs. Moreover, it is possible that the participants' use of public transport was driven by necessity rather than choice and that they were unable to change travel patterns in response to victimization. These findings underscore the importance of targeting public violence toward women and the broader societal norms that limit their participation in public life.

Information-seeking behaviours in Australian sexual minority men engaged in chemsex.

Introduction: Chemsex refers to using illicit substances to facilitate sexual experiences in men who have sex with men. Chemsex has been linked to significant negative impacts on psychological, social, and physical wellbeing. Little is known about information-seeking behaviours in this population. This study aims to provide an in-depth understanding of seeking and engaging with health information. Methods: Self-identified Australian sexual minority men who engage in chemsex (N = 184) participated in an anonymous cross-sectional survey. Variables included chemsex engagement, knowledge, perception and use of harm-reduction information, and associated health and support services. Pearson correlation and ANOVAs were conducted. Wilcoxon-Signed-Rank and Friedman tests were applied to analyse the perceived trustworthiness of information sources. Results: Chemsex represented a meaningful part of sexual events. Most participants knew where to access professional help and harm-reduction information but worried about being judged. Most did not feel comfortable discussing chemsex with health professionals except with sexual health doctors/counsellors. Few users discussed health risks with a professional. Information on chemsex was received through multiple sources with significant differences in perceived relevance and trustworthiness, with sexual health doctors/nurses ranked the most trustworthy information. Interest in non-traditional sources of information was low except for formal peer networks and anonymous personal expert advice. Conclusion: Engagement with health professionals and harm-reduction information is limited in this population, despite high risk and potentially significant adverse health outcomes. Results suggest that new and combined approaches are necessary to reach this population, including peer support networks, anonymous personal advice and changing community attitudes towards chemsex.

Virtual respiratory therapy delivered through a smartphone app: a mixed-methods randomised usability study.

INTRODUCTION: A new smartphone app (QUT Inspire) has been developed to detect inspiratory sound and deliver virtual incentive spirometry (ISy), a respiratory therapy technique used in postoperative recuperation, management of some chronic conditions and with potential applications in SARS-CoV-2 rehabilitation. The aim of this study was to compare the usability of this new app with a clinical ISy device as measured by effectiveness, efficiency and satisfaction. METHODS: In this mixed-methods randomised usability study, healthy volunteers (aged 39.2±12.2 years, n=24) compared inspirations using the QUT Inspire app and a Triflo II clinical ISy device. A post-test questionnaire and a semi-structured interview explored dimensions of usability regarding the new app. RESULTS: The duration of inspirations performed using the QUT Inspire app (7.3±2.0 s) were comparable with use of the Triflo II ISy device (7.5±2.3 s). No artefacts arising from the order of device testing were identified. App users held their phones adjacent but not proximal to their mouths (13.6±6.4 cm), notwithstanding instructions to keep the phone less than 5 cm away for optimal breath sound detection. The use of onscreen text or video instructional materials did not result in a significant reduction in this distance. Participants reported clear preferences for the app (100%, n=24) to motivate persistence with repeated inspirations. App gamification features such as a timer (75%, n=18) and breath counter (83.3%, n=20) were well regarded. Analysis of semi-structured interviews identified four main themes arising from this study: visual reward from responsive app animations, clinical look and feel influencing credibility, perceived effort affecting engagement and selective adoption of gamification features. CONCLUSION: This study demonstrates that a virtual ISy app can be effective, efficient and have high satisfaction. Improvements informed by this research include use of additional phone sensors to optimise sound detection and minimising the distance that phones are held from the user's mouth. Further research in randomised controlled trials are needed to evaluate performance of this app in clinical contexts where ISy is currently employed.

Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine.

Environmental enteric dysfunction is associated with malnutrition as well as infant growth stunting and has been classically defined by villous blunting, decreased crypt-to-villus ratio, and inflammation in the small intestine. Here, we characterized environmental enteric dysfunction among infant rhesus macaques that are naturally exposed to enteric pathogens commonly linked to human growth stunting. Remarkably, despite villous atrophy and histological abnormalities observed in the small intestine, poor growth trajectories and low serum tryptophan levels were correlated with increased histopathology in the large intestine. This work provides insight into the mechanisms underlying this disease and indicates that the large intestine may be an important target for therapeutic intervention.

Smoking in pregnancy and parenting stress: maternal psychological symptoms and socioeconomic status as potential mediating variables.

INTRODUCTION: The purpose of this study was to examine the impact of smoking in pregnancy on parenting stress. Maternal psychological symptoms and socioeconomic status (SES) were evaluated as potential mediating factors between prenatal cigarette use and later parenting stress. METHOD: The sample included 218 mothers who were recruited at the hospital after birth and completed a 6-month visit with their infants at a university laboratory. Based on the mothers' responses to interviews at the hospital on tobacco use during pregnancy, the sample included 77 nonsmokers and 141 smokers. Information on sociodemographic variables, prenatal care, and other substance use during pregnancy was collected at the hospital interview. At the 6-month visit, the mothers completed measures of parenting stress and psychological symptoms. Cotinine levels were assessed at both timepoints. RESULTS: Regression analysis showed that maternal smoking during pregnancy predicted parenting stress in infancy. Maternal symptoms of psychological distress and SES were evaluated simultaneously to determine whether they functioned as mediating variables between smoking in pregnancy and parenting stress. A multiple mediation analysis (Preacher & Hayes, 2008a) showed that maternal psychological symptoms functioned as a mediating variable but that SES did not. CONCLUSIONS: Results suggest that mothers who smoke in pregnancy are likely to experience higher levels of psychological symptoms, which, in turn, predict higher levels of parenting stress. Smoking in pregnancy may be a marker for symptoms of psychological distress in mothers.

Differential activation of insulin receptor substrates 1 and 2 by insulin-like growth factor-activated insulin receptors.

The insulin-like growth factors (insulin-like growth factor I [IGF-I] and IGF-II) exert important effects on growth, development, and differentiation through the IGF-I receptor (IGF-IR) transmembrane tyrosine kinase. The insulin receptor (IR) is structurally related to the IGF-IR, and at high concentrations, the IGFs can also activate the IR, in spite of their generally low affinity for the latter. Two mechanisms that facilitate cross talk between the IGF ligands and the IR at physiological concentrations have been described. The first of these is the existence of an alternatively spliced IR variant that exhibits high affinity for IGF-II as well as for insulin. A second phenomenon is the ability of hybrid receptors comprised of IGF-IR and IR hemireceptors to bind IGFs, but not insulin. To date, however, direct activation of an IR holoreceptor by IGF-I at physiological levels has not been demonstrated. We have now found that IGF-I can function through both splice variants of the IR, in spite of low affinity, to specifically activate IRS-2 to levels similar to those seen with equivalent concentrations of insulin or IGF-II. The specific activation of IRS-2 by IGF-I through the IR does not result in activation of the extracellular signal-regulated kinase pathway but does induce delayed low-level activation of the phosphatidylinositol 3-kinase pathway and biological effects such as enhanced cell viability and protection from apoptosis. These findings suggest that IGF-I can function directly through the IR and that the observed effects of IGF-I on insulin sensitivity may be the result of direct facilitation of insulin action by IGF-I costimulation of the IR in insulin target tissues.

Assessment of Mobile Health Apps Using Built-In Smartphone Sensors for Diagnosis and Treatment: Systematic Survey of Apps Listed in International Curated Health App Libraries.

BACKGROUND: More than a million health and well-being apps are available from the Apple and Google app stores. Some apps use built-in mobile phone sensors to generate health data. Clinicians and patients can find information regarding safe and effective mobile health (mHealth) apps in third party-curated mHealth app libraries. OBJECTIVE: These independent Web-based repositories guide app selection from trusted lists, but do they offer apps using ubiquitous, low-cost smartphone sensors to improve health? This study aimed to identify the types of built-in mobile phone sensors used in apps listed on curated health app libraries, the range of health conditions these apps address, and the cross-platform availability of the apps. METHODS: This systematic survey reviewed three such repositories (National Health Service Apps Library, AppScript, and MyHealthApps), assessing the availability of apps using built-in mobile phone sensors for the diagnosis or treatment of health conditions. RESULTS: A total of 18 such apps were identified and included in this survey, representing 1.1% (8/699) to 3% (2/76) of all apps offered by the respective libraries examined. About one-third (7/18, 39%) of the identified apps offered cross-platform Apple and Android versions, with a further 50% (9/18) only dedicated to Apple and 11% (2/18) to Android. About one-fourth (4/18, 22%) of the identified apps offered dedicated diagnostic functions, with a majority featuring therapeutic (9/18, 50%) or combined functionality (5/18, 28%). Cameras, touch screens, and microphones were the most frequently used built-in sensors. Health concerns addressed by these apps included respiratory, dermatological, neurological, and anxiety conditions. CONCLUSIONS: Diligent mHealth app library curation, medical device regulation constraints, and cross-platform differences in mobile phone sensor architectures may all contribute to the observed limited availability of mHealth apps using built-in phone sensors in curated mHealth app libraries. However, more efforts are needed to increase the number of such apps on curated lists, as they offer easily accessible low-cost options to assist people in managing clinical conditions.

Meat, Masculinity, and Health for the "Typical Aussie Bloke": A Social Constructivist Analysis of Class, Gender, and Consumption.

Food choice is complex and influenced by a range of social, environmental, structural, and individual factors. Poor diet is one of the major contributors to the burden of disease, in particular for men who habitually have lower intakes of fruits and vegetables and higher intakes of meat. Food choice has been linked to the expression of masculine identities. This research used a Bourdieusian framework to explore the influential drivers of young Australian men's eating habits based on occupational groupings. Twenty men aged 19-30 years participated in in-depth semistructured interviews. Analysis used a grounded theory, social constructivist approach and identified five themes: performative masculinities and meat; meat cuts across social class; the influence of masculine autonomy on dietary choice; women protecting Australian men's health; and the role of environmental and structural barriers. These results indicated that habitus remains a useful conceptual framework to explain the results, and cultural capital is reinforced as a phenomenon. Occupation and gender appear to no longer be primary drivers of food choice in this group of men. Rather there is a shift toward an understanding of multiple masculinities and the development of microcultures with interactions between structure and agency. Meat still features in the food world of Australian men, but there are shifts to deprioritize its importance. There needs to be a more nuanced understanding of the importance of autonomy and control as well as the role of women in relation to men's dietary intakes and how this can be harnessed for positive dietary change.

Early overnutrition alters synaptic signaling and induces leptin resistance in arcuate proopiomelanocortin neurons.

Early overnutrition disrupts leptin sensitivity and the development of hypothalamic pathways involved in the regulation of metabolism and feeding behavior. While previous studies have largely focused on the development of neuronal projections, few studies have examined the impact of early nutrition on hypothalamic synaptic physiology. In this study we characterized the synaptic development of proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH), their sensitivity to leptin, and the impact of early overnutrition on the development of these neurons. Electrophysiology recordings were performed in mouse ARH brain slices containing POMC-EGFP neurons from postnatal age (P) 7-9 through adulthood. We determined that pre- and postsynaptic components of inhibitory inputs increased throughout the first 3 weeks of the postnatal period, which coincided with a decreased membrane potential in POMC neurons. We then examined whether chronic postnatal overnutrition (CPO) altered these synaptic connections. CPO mice exhibited increased body weight and circulating leptin levels, as described previously. POMC neurons in CPO mice had an increase in post-synaptic inhibitory currents compared to controls at 2 weeks of age, but this effect reversed by the third week. In control mice we observed heterogenous effects of leptin on POMC neurons in early life that transitioned to predominantly stimulatory actions in adulthood. However, postnatal overfeeding resulted in POMC neurons becoming leptin-resistant which persisted into adulthood. These studies suggest that postnatal overfeeding alters the postsynaptic development of POMC neurons and induces long-lasting leptin resistance in ARH-POMC neurons.

Reelin is modulated by diet-induced obesity and has direct actions on arcuate proopiomelanocortin neurons.

OBJECTIVE: Reelin (RELN) is a large glycoprotein involved in synapse maturation and neuronal organization throughout development. Deficits in RELN signaling contribute to multiple psychological disorders, such as autism spectrum disorder, schizophrenia, and bipolar disorder. Nutritional stress alters RELN expression in brain regions associated with these disorders; however, the involvement of RELN in the neural circuits involved in energy metabolism is unknown. The RELN receptors apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) are involved in lipid metabolism and expressed in the hypothalamus. Here we explored the involvement of RELN in hypothalamic signaling and the impact of diet-induced obesity (DIO) on this system. METHODS: Adult male mice were fed a chow diet or maintained on a high-fat diet (HFD) for 12-16 weeks. HFD-fed DIO mice exhibited decreased ApoER2 and VLDLR expression and increased RELN protein in the hypothalamus. Electrophysiology was used to determine the mechanism by which the central fragment of RELN (CF-RELN) acts on arcuate nucleus (ARH) satiety-promoting proopiomelanocortin (POMC) neurons and the impact of DIO on this circuitry. RESULTS: CF-RELN exhibited heterogeneous presynaptic actions on inhibitory inputs onto ARH-POMC-EGFP neurons and consistent postsynaptic actions. Additionally, central administration of CF-RELN caused a significant increase in ARH c-Fos expression and an acute decrease in food intake and body weight. CONCLUSIONS: We conclude that RELN signaling is modulated by diet, that RELN is involved in synaptic signaling onto ARH-POMC neurons, and that altering central CF-RELN levels can impact food intake and body weight.

Do people with intersecting identities report more high-risk alcohol use and lifetime substance use?

OBJECTIVES: We examined protective and non-protective effects of disadvantaged social identities and their intersections on lifetime substance use and risky alcohol consumption. METHODS: Data from 90,941 participants of the Global Drug Survey 2015 were analysed. Multivariable logistic regressions were used to calculate adjusted odds ratios for lifetime use of nine psychoactive substances, as well as high-risk/harmful alcohol use. Disadvantaged identities from three categories (ethnicity, sexual identity, gender), and interactions between these were compared. RESULTS: Findings indicate that participants with disadvantaged ethnic and sexual minority identities are more likely to use psychoactive substances compared to their counterparts. The intersecting identity 'disadvantaged ethnic identity and sexual minority' appears to be protective compared to those with just one of these identities. While female gender appears to be highly protective in general, it is not protective among females with disadvantaged social identities. CONCLUSIONS: Stark disparities in substance use between different social identities and their intersections emphasise the importance of intersectionality theories in public health research intervention design. Future research on health equity, particularly substance use, should target individuals with intersecting identities.

Differential activation of insulin receptor isoforms by insulin-like growth factors is determined by the C domain.

The actions of IGF-I and IGF-II are thought to be largely due to their activation of the IGF-I receptor. However, IGF-II can also bind with high affinity to, and effectively activate, an isoform of the insulin receptor (IR-A) that lacks a sequence at the carboxyl-terminal end of the extracellular alpha subunit due to the alternative splicing of exon 11. This isoform is poorly activated by IGF-I. Here, we show that IGF-II, but not IGF-I, induces potent autophosphorylation of residues Y1158, Y1162, and Y1163 in the activation loop of the kinase domain and tyrosine 960 in the juxtamembrane region of both IR-A and IR-B (exon 11+) isoforms. We have also found, by using IGF chimeras, that the C domain of IGF-II completely accounts for the ability of IGF-II to stimulate IR autophosphorylation compared with IGF-I. We further show that the C domains are responsible for the differential abilities of IGF-II and IGF-I to activate phosphorylation of insulin receptor substrate-1 and Akt, as well as their ability to induce migration and cell survival via the IR-A. Finally, we show for the first time that IGF signaling through the IR-A can protect cells from butyrate-induced apoptosis. In summary, our studies define the structural determinants that allow potent IGF-II signaling and regulation of cellular functions through the IR-A and provide novel insights into IGF signaling via the IR.

A novel, stable, aqueous glucagon formulation using ferulic acid as an excipient.

Commercial glucagon is unstable due to aggregation and degradation. In closed-loop studies, it must be reconstituted frequently. For use in a portable pump for 3 days, a more stable preparation is required. At alkaline pH, curcumin inhibited glucagon aggregation. However, curcumin is not sufficiently stable for long-term use. Here, we evaluated ferulic acid, a stable breakdown product of curcumin, for its ability to stabilize glucagon. Ferulic acid-formulated glucagon (FAFG), composed of ferulic acid, glucagon, L-methionine, polysorbate-80, and human serum albumin in glycine buffer at pH 9, was aged for 7 days at 37°C. Glucagon aggregation was assessed by transmission electron microscopy (TEM) and degradation by high-performance liquid chromatography (HPLC). A cell-based protein kinase A (PKA) assay was used to assess in vitro bioactivity. Pharmacodynamics (PD) of unaged FAFG, 7-day aged FAFG, and unaged synthetic glucagon was determined in octreotide-treated swine. No fibrils were observed in TEM images of fresh or aged FAFG. Aged FAFG was 94% intact based on HPLC analysis and there was no loss of bioactivity. In the PD swine analysis, the rise over baseline of glucose with unaged FAFG, aged FAFG, and synthetic native glucagon (unmodified human sequence) was similar. After 7 days of aging at 37°C, an alkaline ferulic acid formulation of glucagon exhibited significantly less aggregation and degradation than that seen with native glucagon and was bioactive in vitro and in vivo. Thus, this formulation may be stable for 3-7 days in a portable pump for bihormonal closed-loop treatment of T1D.

Saw palmetto extract suppresses insulin-like growth factor-I signaling and induces stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation in human prostate epithelial cells.

A common alternative therapy for benign prostatic hyperplasia (BPH) is the extract from the fruit of saw palmetto (SPE). BPH is caused by nonmalignant growth of epithelial and stromal elements of the prostate. IGF action is important for prostate growth and development, and changes in the IGF system have been documented in BPH tissues. The main signaling pathways activated by the binding of IGF-I to the IGF-I receptor (IGF-IR) are the ERK arm of the MAPK cascade and the phosphoinositol-3-kinase (PI3K)/protein kinase B (PKB/Akt) cascade. We tested the hypothesis that SPE suppresses growth and induces apoptosis in the P69 prostate epithelial cell line by inhibiting IGF-I signaling. Treatment with 150 microg/ml SPE for 24 h decreased IGF-I-induced proliferation of P69 cells and induced cleavage of the enzyme poly(ADP-ribose)polymerase (PARP), an index of apoptosis. Treatment of serum-starved P69 cells with 150 microg/ml SPE for 6 h reduced IGF-I-induced phosphorylation of Akt (assessed by Western blot) and Akt activity (assessed by an Akt kinase assay). Western blot analysis showed that SPE reduced IGF-I-induced phosphorylation of the adapter protein insulin receptor substrate-1 and decreased downstream effects of Akt activation, including increased cyclin D1 levels and phosphorylation of glycogen synthase kinase-3 and p70(s6k). There was no effect on IGF-I-induced phosphorylation of MAPK, IGF-IR, or Shc. Treatment of starved cells with SPE alone induced phosphorylation the proapoptotic protein JNK. SPE treatment may relieve symptoms of BPH, in part, by inhibiting specific components of the IGF-I signaling pathway and inducing JNK activation, thus mediating antiproliferative and proapoptotic effects on prostate epithelia.

Smoking cessation, maintenance, and relapse experiences among pregnant and postpartum adolescents: a qualitative analysis.

PURPOSE: To understand the experiences and processes of smoking cessation, maintenance, and relapse for pregnant and postpartum adolescents, whose perspectives and needs might be different from other age groups. METHODS: We conducted in-depth semistructured interviews with 52 pregnant and postpartum adolescents using tools of grounded theory analysis. RESULTS: Spontaneous smoking cessation during pregnancy was reported by most participants. This was generally explained as resulting from knowledge about the harmful effects of tobacco on the fetus, intense emotional reactions to this knowledge, or unpleasant tobacco- and pregnancy-related physical symptoms. Relapses were common, however. Most participants experienced guilt when they relapsed during pregnancy. Postpartum relapse was less fraught, as many participants no longer considered their smoking to negatively affect their infants. This was found even among adolescents who were breastfeeding. Participants who did maintain cessation postpartum typically reported support from smoke-free families and environments. CONCLUSIONS: The results of this study suggest a constellation of protective factors that contribute to smoking cessation and maintenance during and after pregnancy, as well as risk factors that contribute to temporary or permanent relapses. These results can inform future research and interventions on tobacco prevention among pregnant and postpartum adolescents. Several promising strategies for intervention development are discussed.