A process evaluation of Promotional Guides used by health visitors to support men's transition to fatherhood: a qualitative study.

BACKGROUND: Health visitors play an important role in supporting new parents in their transition to parenthood. A programme known as the Promotional Guide system is used by many health visitors in England with mothers and fathers to support this transition, but there is little known about health visitors' views of the Promotional Guides, how they are used in practice or barriers to effective implementation with fathers. AIMS: The aim of this study was to explore the following: (1) health visitors' use of Promotional Guides with fathers, (2) health visitors' assessment of father's mental health and wellbeing and (3) facilitators and barriers to using Promotional Guides in practice. METHODS: A prospective observational cohort study and a process evaluation informed by the Medical Research Council guidance were conducted. A purposive sample of 11 health visitors was interviewed, and an additional seven were observed using the Promotional Guides in practice. Data were analysed using framework analysis. RESULTS: Five main themes were identified from interview and observational data as follows: (1) Enquiry into fathers' mental health, (2) Promotional Guides in practice, (3) health visitors' perceptions of the Promotional Guides system, (4) barriers to using Promotional Guides with fathers and (5) facilitators and recommendations for using Promotional Guides with fathers. This study identified a number of barriers and facilitators to the use of Promotional Guides with fathers. Recommendations were made for improving services for first-time fathers, implementing the Promotional Guide system with fathers and highlighting areas for future research. CONCLUSION: This study considered the acceptability, feasibility and fidelity of using the Promotional Guide programme with fathers from the health visitor's perspective. The findings provided an insight into health visitors' experiences of working with fathers, inquiring about men's mental health needs and their use of the Promotional Guides with men during the perinatal period.

The bacterial community of Quesnel Lake sediments impacted by a catastrophic mine tailings spill differ in composition from those at undisturbed locations - two years post-spill.

The West Basin of Quesnel Lake (British Columbia, Canada) suffered a catastrophic disturbance event in August 2014 when mine tailings and scoured natural material were deposited into the lake's West Basin due to an impoundment failure at the adjacent Mount Polley copper-gold mine. The deposit covered a significant portion of the West Basin floor with a thick layer of material. Since lake sediments host bacterial communities that play key roles in the geochemical cycling in lacustrine environments, it is important to understand which groups inhabit the newly deposited material and what this implies for the ecological function of the West Basin. Here we report a study conducted two years post-spill, comparing the bacterial communities from sediments of both disturbed and undisturbed sites. Our results show that sediments from disturbed sites differed in physical and chemical properties than those in undisturbed sites (e.g. higher pH, particle size and Cu concentration). Furthermore, bacterial communities from the disturbed sites appeared to be legacy communities from the tailings impoundment, with metabolic potential revolving mainly around the cycling of S and metals, whereas the ones from the undisturbed sites were associated with the cycling of N.

Spherical-supported membranes as platforms for screening against membrane protein targets.

Screening assays performed against membrane protein targets (e.g. phage display) are hampered by issues arising from protein expression and purification, protein stability in detergent solutions and epitope concealment by detergent micelles. Here, we have studied a fast and simple method to improve screening against membrane proteins: spherical-supported bilayer lipid membranes ("SSBLM"). SSBLMs can be quickly isolated via low-speed centrifugation and redispersed in liquid solutions while presenting the target protein in a native-like lipid environment. To provide proof-of-concept, SSBLMs embedding the polytopic bacterial nucleoside transporter NupC were assembled on 100- and 200 nm silica particles. To test specific binding of antibodies, NupC was tagged with a poly-histidine epitope in one of its central loops between two transmembrane helices. Fluorescent labelling, small angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-EM) were used to monitor formation of the SSBLMs. Specific binding of an anti-his antibody and a gold-nitrilotriacetic acid (NTA) conjugate probe was confirmed with ELISAs and cryo-EM. SSBLMs for screening could be made with purified and lipid reconstituted NupC, as well as crude bacterial membrane extracts. We conclude that SSBLMs are a promising new means of presenting membrane protein targets for (biomimetic) antibody screening in a native-like lipid environment.

NDRG4, an early detection marker for colorectal cancer, is specifically expressed in enteric neurons.

BACKGROUND: Promoter methylation of N-myc Downstream-Regulated Gene 4 (NDRG4) in fecal DNA is an established early detection marker for colorectal cancer (CRC). Despite its connection to CRC, NDRG4 is predominantly studied in brain and heart, with little to no knowledge about its expression or role in other organs. In this study, we aimed to determine the whole-body expression of NDRG4, with a focus on the intestinal tract. METHODS: We investigated NDRG4 expression throughout the body by immunohistochemistry, Western Blotting and in situ mRNA hybridization using tissues from NDRG4 wild-type, heterozygous and knockout mice and humans. In addition, we explored cell-specific expression of NDRG4 in murine whole-mount gut preparations using immunofluorescence and confocal microscopy. KEY RESULTS: NDRG4 is specifically expressed within nervous system structures throughout the body. In the intestinal tract of both mouse and man, NDRG4 immunoreactivity was restricted to the enteric nervous system (ENS), where it labeled cell bodies of the myenteric and submucosal plexuses and interconnecting nerve fibers. More precisely, NDRG4 expression was limited to neurons, as NDRG4 always co-localized with HuC/D (pan-neuronal marker) but never with GFAP (an enteric glial cell marker). Furthermore, NDRG4 was expressed in various neuropeptide Y positive neurons, but was only found in a minority (~10%) of neurons expressing neuronal nitric oxide synthase. CONCLUSIONS AND INFERENCES: NDRG4 is exclusively expressed by central, peripheral and enteric neurons/nerves, suggesting a neuronal-specific role of this protein. Our findings raise the question whether NDRG4, via the ENS, an understudied component of the tumor microenvironment, supports CRC development and/or progression.

Student learning styles in anatomy and physiology courses: Meeting the needs of nursing students.

Anatomy and Physiology is a core course in pre-registration nursing programs, yet many students have difficulty successfully negotiating the large volume of content and the complex concepts in these bioscience courses. Typically students perform poorly in these 'threshold' courses', despite multiple interventions to support student engagement. Investigation of the shortcomings in these courses, based on feedback from students indicated several key areas of difficulty in the course, especially focused around a relative lack of hands-on 'concrete' activities in laboratories and tutorials. To attempt to address this, academic and technical staff developed activities for students that promoted discussion and allowed students to interact easily and repetitively with content. Interactive tables and posters that needed to be labelled or 'filled-in' using pre-prepared Velcro dots, as well as pre-prepared flash cards to promote group work, were some examples of the activities used to enhance student experiences and promote hands-on learning. Over the academic year of 2013 these activities were introduced into the laboratory and tutorial classes for first year Bachelor of Nursing anatomy and physiology students. Staff and student participants positively rated implementation of these new activities on surveys, as they allowed them to explore the difficult aspects of anatomy and physiology, utilising various learning styles that may have been neglected in the past.

Social support and religion: mental health service use and treatment of schizophrenia.

The perceptions and religious beliefs held by family members, mental health and health care professionals, and the community may affect the treatment of individuals with schizophrenia. To better identify and understand the influence of families, professionals and community members on individual's treatment for schizophrenia, this review paper examines: (1) the religious perceptions of families, professionals, and the public towards schizophrenia; (2) religious perceptions of the etiology of schizophrenia; (3) how others perceive religion as a coping mechanism; and (4) how religion influences treatment engagement and help-seeking behaviors. MEDLINE and PsycInfo databases were systematically searched from 1980 to 2010 using the terms schizophrenia, schizoaffective, schizophreniform, psychotic disorder not otherwise specified and religion, religiosity, spirituality, and faith. Forty-three (n = 43) original research studies met the inclusion criteria. This study found that religious beliefs influence the treatment of schizophrenia in the following ways: Religious themes were positively associated with coping, treatment engagement and help-seeking behavior. Evidence of religious underpinnings was found in perceptions of etiology. The findings also indicate that there is often both a preference among family members and caregivers to utilize religious-based professionals and caution toward mental health professionals. Researchers and professionals may find avenues for improving treatment through examining the interaction of religious and schizophrenia at the social support level.

Toxicity-structure activity evaluation of limonoids from Swietenia species on Artemia salina.

CONTEXT: Many plant extracts and compounds are being investigated for their cytotoxicity and hence their medicinal or therapeutic properties. Reports of toxicity studies with limonoid analogs have been sparse and have involved mainly crude extracts. In this study, individual natural limonoids have been isolated and their toxicity manipulated via semisynthesis. OBJECTIVE: The lethality of limonoid analogs from Swietenia macrophylla King and Swietenia aubrevilleana Stehlé & Cusin (Meliaceae) against Artemia salina Leach was determined. MATERIALS AND METHODS: Four known natural limonoids were isolated from the dry ground seeds of S. macrophylla and S. aubrevilleana, modified using acylation and hydrolysis reactions and tested in A. salina lethality assays at 1-400 ppm. A 50% lethal concentration (LC(50)) was determined by probit analysis. RESULTS: Higher levels of toxicity were achieved in most of the prepared analogs compared with the parent natural limonoids. The compound showing the highest toxicity with LC(50) 3.9 ppm was 3-O-benzoyl-3-detigloylisoswietenine (20). Other analogs with high toxicity were 6-O-benzoylswietenolide (7), 6-O-benzoylswietenine (17), and 3,6-O,O-dipropionylswietenolide (9), which showed LC(50) values of 4.3, 7.5, and 28.5 ppm, respectively. DISCUSSION AND CONCLUSIONS: Toxicity can be improved via semisynthesis. The compounds exhibiting high toxicity (low LC(50)) may be good candidates for cytotoxicity studies.

Limonoids from Meliaceae with lipid peroxidation inhibitory activity.

In this study the antioxidant activity of natural limonoids from Meliaceae swietenolide (1), 3,6-O,O-diacetylswietenolide (2), swietenine (3), swietemahonin G (4) and 2-hydroxyswietenine (5) were investigated along with the semi-synthetic analogues (6-25) of compounds 1, 3-4. Lipid peroxidation (LPO) inhibitory assays revealed 85.6, 13.3, 77.3, 61.2 and 24.6% inhibition for the natural compounds 1-5. Excellent antioxidant activity was seen for the semi-synthetic analogues 10 (98.3%), 16-17, 21-22 and 25 (100%), which were more active than the positive controls BHA (91.3%) and TBHQ (95.7%).

Human equilibrative nucleoside transporter (ENT) family of nucleoside and nucleobase transporter proteins.

1. The human (h) SLC29 family of integral membrane proteins is represented by four members, designated equilibrative nucleoside transporters (ENTs) because of the properties of the first-characterized family member, hENT1. They belong to the widely distributed eukaryotic ENT family of equilibrative and concentrative nucleoside/nucleobase transporter proteins. 2. A predicted topology of eleven transmembrane helices has been experimentally confirmed for hENT1. The best-characterized members of the family, hENT1 and hENT2, possess similar broad permeant selectivities for purine and pyrimidine nucleosides, but hENT2 also efficiently transports nucleobases. hENT3 has a similar broad permeant selectivity for nucleosides and nucleobases and appears to function in intracellular membranes, including lysosomes. 3. hENT4 is uniquely selective for adenosine, and also transports a variety of organic cations. hENT3 and hENT4 are pH sensitive, and optimally active under acidic conditions. ENTs, including those in parasitic protozoa, function in nucleoside and nucleobase uptake for salvage pathways of nucleotide synthesis and, in humans, are also responsible for the cellular uptake of nucleoside analogues used in the treatment of cancers and viral diseases. 4. By regulating the concentration of adenosine available to cell surface receptors, mammalian ENTs additionally influence physiological processes ranging from cardiovascular activity to neurotransmission.

Treatment of log yard runoff using a r-circulating sand filtration process.

A re-circulating filtration process using oxide-coated sand successfully removed COD and turbidity from log yard runoff. After passing only one pore volume of the runoff through the sand column, 72% COD was removed. The 2.4% Fe and Al oxide coating on the sand contributed to better COD removal than was obtained when the sand was stripped of oxide coating (86% versus 52%, respectively), at least initially before saturation of adsorption sites on the oxide coating occurred. The best COD removal performance came from conditioned sand. This sand, from the same original source and identical to the oxide-coated sand used in all experiments, came from an existing experimental sand column that had been treating log yard runoff for 1 year. The "conditioning" resulted in the sand having a higher TOC content (0.26% wt) and smaller particle sizes. This sand was able to consistently remove 80% COD from repeated batches of log yard runoff with strengths up to 3690 mg l(-1).

Properties of an entropy-based signal receiver with an application to ultrasonic molecular imaging.

Qualitative and quantitative properties of the finite part, H(f), of the Shannon entropy of a continuous waveform f(t) in the continuum limit are derived in order to illuminate its use for waveform characterization. Simple upper and lower bounds on H(f), based on features of f(t), are defined. Quantitative criteria for a priori estimation of the average-case variation of H(f) and log E(f), where E(f) is the signal energy of f(t) are also derived. These provide relative sensitivity estimates that could be used to prospectively choose optimal imaging strategies in real-time ultrasonic imaging machines, where system bandwidth is often pushed to its limits. To demonstrate the utility of these sensitivity relations for this application, a study designed to assess the feasibility of identification of angiogenic neovasculature targeted with perfluorocarbon nanoparticles that specifically bind to alpha(v)beta3-integrin expression in tumors was performed. The outcome of this study agrees with the prospective sensitivity estimates that were used for the two receivers. Moreover, these data demonstrate the ability of entropy-based signal receivers when used in conjunction with targeted nanoparticles to elucidate the presence of alpha(v)beta3 integrins in primordial neovasculature, particularly in acoustically unfavorable environments.

Paying research participants: a study of current practices in Australia.

OBJECTIVE: To examine current research payment practices and to inform development of clearer guidelines for researchers and ethics committees. DESIGN: Exploratory email based questionnaire study of current research participant reimbursement practices. A diverse sample of organisations and individuals were targeted. SETTING: Australia. PARTICIPANTS: Contacts in 84 key research organisations and select electronic listservers across Australia. A total of 100 completed questionnaires were received with representations from a variety of research areas (for example, market, alcohol and drug, medical, pharmaceutical and social research). MAIN MEASUREMENTS: Open-ended and fixed alternative questions about type of research agency; type of research; type of population under study; whether payment is standard; amounts and mechanisms of payment; factors taken into account when deciding on payment practices; and whether payment policies exist. RESULTS: Reimbursement practice is highly variable. Where it occurs (most commonly for drug dependent rather than health professional or general population samples) it is largely monetary and is for time and out-of-pocket expenses. Ethics committees were reported to be often involved in decision making around reimbursement. CONCLUSIONS: Research subject payment practices vary in Australia. Researchers who do provide payments to research participants generally do so without written policy and procedures. Ethics committees have an important role in developing guidelines in this area. Specific guidelines are needed considering existing local policies and procedures; payment models and their application in diverse settings; case study examples of types and levels of reimbursement; applied definitions of incentive and inducement; and the rationale for diverse payment practices in different settings.

Synaptogenesis in the hippocampal CA1 field following traumatic brain injury.

Traumatic brain injury (TBI) results in both acute and chronic disruption of cognitive ability that may be mediated through a disruption of hippocampal circuitry. Experimental models of TBI have demonstrated that cortical contusion injuries can result in the loss of specific neurons in the CA3 subfield of the ipsilateral hippocampus, resulting in partial loss of afferents to the CA1 subfield. Numerous studies have documented the ability of the central nervous system to compensate for deafferentation by initiating a plasticity response capable of restoring lost synaptic contacts. The present study was designed to examine the time course of loss and replacement of synaptic contacts in stratum radiatum dendritic field of CA1. Young adult rats were subjected to a lateral cortical contusion injury and assayed for total synaptic numbers using unbiased stereology coupled with transmission electron microscopy. Injured animals demonstrated a 60% loss of synapses in CA1 at 2 days post-injury, followed by a reinnervation process that was apparent as early as 10 days post-injury. By 60 days post-injury, total synaptic numbers had approached pre-injury levels but were still significantly lower. Some animals were behaviorally tested for spatial memory in a Morris Water Maze at 15 and 30 days post-injury. While there was some improvement in spatial memory, injured animals continued to demonstrate a significant deficit in acquisition. These results show that the hippocampus ipsilateral to the cortical contusion is capable of a significant plasticity response but that synapse replacement in this area does not necessarily result in significant improvement in spatial learning.

Adenosine contributes to mu-opioid synaptic inhibition in rat substantia gelatinosa in vitro.

The purpose of this study was to investigate the cellular basis of the synergistic anti-nociceptive interaction between adenosine and opioids reported for spinal cord in vivo. Patch clamp recordings from rat substantia gelatinosa neurons in vitro were used to assess whether adenosine receptor antagonists impact upon mu-opioid receptor (MOR)-mediated inhibition of glutamatergic synaptic transmission. The MOR agonist DAMGO inhibited evoked EPSCs and this inhibition was partly reversed by DPCPX, an A1 receptor (A1R) antagonist. The A2a receptor antagonist, ZM241385 had mixed effects on DAMGO-mediated inhibition, producing either a further inhibition or a reversal of the inhibition. These data show that activation of A1R as a secondary consequence of MOR-activation and putative adenosine release will potentiate opioid synaptic inhibition of nociceptive circuitry.

Chlamydial infection in women along the US-Mexico border.

Few studies have reported on sexually transmitted infections at the US-Mexico border, so the prevalence of Chlamydia trachomatis in this population remains uncertain. This binational project investigated the prevalence of, and risk factors for, C. trachomatis among women along the Arizona, US-Sonora, Mexico border. Women who self-referred for routine gynaecological care were invited to complete an interviewer-administered questionnaire and to undergo a Pap smear, C. trachomatis test, and HPV test. In 2270 women, C. trachomatis prevalence overall was 8.2% as measured by hybrid capture and 2.6% by enzyme immunoassay. Infection was associated with young age, a history of new sexual partner(s) in the previous three months, HPV infection, and proximity of clinic to the international border. Antibiotic use in the previous 30 days was associated with decreased odds of infection. Women in Arizona-Sonora border communities are at increased risk for C. trachomatis infection compared to women attending clinics in non-border locations.

Chloroplast mutations induced by 9-aminoacridine hydrochloride are independent of the plastome mutator in Oenothera.

Oenothera plants homozygous for the recessive plastome mutator allele ( pm) show chloroplast DNA (cpDNA) mutation frequencies that are about 1,000-fold higher than spontaneous levels. The pm-encoded gene product has been hypothesized to have a function in cpDNA replication, repair and/or mutation avoidance. Previous chemical mutagenesis experiments with the alkylating agent nitroso-methyl urea (NMU) showed a synergistic effect of NMU on the induction of mutations in the pm line, suggesting an interaction between the pm-encoded gene product and one of the repair systems that corrects alkylation damage. The goal of the experiments described here was to examine whether the pm activity extends to the repair of damage caused by non-alkylating mutagens. To this end, the intercalating mutagen, 9-aminoacridine hydrochloride (9AA) was tested for synergism with the plastome mutator. A statistical analysis of the data reported here indicates that the pm-encoded gene product is not involved in the repair of the 9AA-induced mutations. However, the recovery of chlorotic sectors in plants derived from the mutagenized seeds shows that 9AA can act as a mutagen of the chloroplast genome.

Coupling of CFTR-mediated anion secretion to nucleoside transporters and adenosine homeostasis in Calu-3 cells.

The purpose of this study was to characterize the role of adenosine-dependent regulation of anion secretion in Calu-3 cells. RT-PCR studies showed that Calu-3 cells expressed mRNA for A2A and A2B but not A1 or A3 receptors, and for hENT1, hENT2 and hCNT3 but not hCNT1 or hCNT2 nucleoside transporters. Short-circuit current measurements indicated that A2B receptors were present in both apical and basolateral membranes, whereas A2A receptors were detected only in basolateral membranes. Uptake studies demonstrated that the majority of adenosine transport was mediated by hENT1, which was localized to both apical and basolateral membranes, with a smaller hENT2-mediated component in basolateral membranes. Whole-cell current measurements showed that application of extracellular nitrobenzylmercaptopurine ribonucleoside (NBMPR), a selective inhibitor of hENT1-mediated transport, had similar effects on whole-cell currents as the application of exogenous adenosine. Inhibitors of adenosine kinase and 5'-nucleotidase increased and decreased, respectively, whole-cell currents, whereas inhibition of adenosine deaminase had no effect. Single-channel studies showed that NBMPR and adenosine kinase inhibitors activated CFTR Cl- channels. These results suggested that the equilibrative nucleoside transporters (hENT1, hENT2) together with adenosine kinase and 5'-nucleotidase play a crucial role in the regulation of CFTR through an adenosine-dependent pathway in human airway epithelia.

New erythrolides from the Caribbean gorgonian octocoral Erythropodium caribaeorum.

Seven new briarane diterpenes, erythrolides K-Q (1-7), as well as the known compounds erythrolides A, B, C, F, and J have been isolated from samples of the Caribbean gorgonian Erythropodium caribaeorumcollected at Buccoo Reef and Flying Reef, Tobago. The structures of the new compounds were determined by high-resolution 1H and 13C NMR spectroscopy utilizing COSY, HMBC, HMQC, and NOESY experiments. The structures of erythrolides K and P were confirmed and their relative stereochemistry determined by X-ray crystallographic analysis.

Immunocytochemical demonstration of the equilibrative nucleoside transporter rENT1 in rat sinoatrial node.

Adenosine exerts multiple receptor-mediated effects in the heart, including a negative chronotropic effect on the sinoatrial node. The aim of this study was to investigate the distribution of the equilibrative nucleoside transporter rENT1 in rat sinoatrial node and atrial muscle. Immunocytochemistry and/or immunoblotting revealed abundant expression of this protein in plasma membranes of sinoatrial node and in atrial and ventricular cells. Because rENT1-mediated transport is likely to regulate the local concentrations of adenosine in the sinoatrial node and other parts of the heart, it represents a potential pharmacological target that might be exploited to ameliorate ischemic damage during heart surgery.

Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers.

UNLABELLED: Elevated levels of choline (trimethyl-2-hydroxyethylammonium) and choline kinase (CK) activity in neoplasms have motivated the development of positron-labeled choline analogs for noninvasive detection of cancer using PET. The aim of this study was to further evaluate [(18)F]fluorocholine (fluoromethyl-dimethyl-2-hydroxyethylammonium [FCH]) as an oncologic probe in comparison with several other closely related molecules. METHODS: FCH, [(18)F]fluoromethyl-methylethyl-2-hydroxyethylammonium (FMEC), [(18)F]fluoroethyl-dimethyl-2-hydroxyethylammonium (FEC), and [(18)F]fluoropropyl-dimethyl-2-hydroxyethylammonium (FPC) were synthesized through [(18)F]fluoroalkylation reactions. In vitro phosphorylation rates of the (18)F-labeled choline analogs and [methyl-(14)C]choline (CH) were studied using yeast CK. Several choline radiotracers were also evaluated in cultured PC-3 human prostate cancer cells. Data on chemical stability, radiation dosimetry, and toxicity of FCH were obtained. PET studies with FCH were performed on a patient with prostate cancer and a patient with a brain tumor. RESULTS: FCH and FMEC revealed in vitro phosphorylation by CK that was similar to that of choline, whereas rates of phosphorylation of FEC and FPC were 30% (P < 0.01) and 60% (P < 0.01) lower, respectively. Accumulations of FCH, CH, and FPC in cultured PC-3 cancer cells were comparable, whereas uptake of FEC was approximately one fifth that of FCH. Dosimetry estimates using FCH biodistribution data in mice indicated that the kidneys are radiation-dose-critical organs for FCH. PET images of a patient with recurrent prostate cancer showed uptake of FCH in the prostatic bed and in metastases to lymph nodes. FCH PET showed uptake in malignancies in a patient with metastatic breast cancer. PET revealed FCH uptake in biopsy-proven recurrent brain tumor with little confounding uptake by normal brain tissues. CONCLUSION: The fluoromethyl choline analog FCH may serve as a probe of choline uptake and phosphorylation in cancer cells, whereas fluoroethyl (FEC) and fluoropropyl (FPC) analogs appear to have relatively poorer biologic compatibility. Preliminary PET studies on patients with prostate cancer and with breast cancer and brain tumor support further studies to evaluate the usefulness of FCH as an oncologic probe.