Publications by authors named "Michelle Lam"

25 Publications

  • Page 1 of 1

An artificial intelligence that increases simulated brain-computer interface performance.

J Neural Eng 2021 05 13;18(4). Epub 2021 May 13.

Department of Electrical and Computer Engineering, University of California, Los Angeles, CA 90024, United States of America.

Brain-computer interfaces (BCIs) translate neural activity into control signals for assistive devices in order to help people with motor disabilities communicate effectively. In this work, we introduce a new BCI architecture that improves control of a BCI computer cursor to type on a virtual keyboard.Our BCI architecture incorporates an external artificial intelligence (AI) that beneficially augments the movement trajectories of the BCI. This AI-BCI leverages past user actions, at both long (100 s of seconds ago) and short (100 s of milliseconds ago) timescales, to modify the BCI's trajectories.We tested our AI-BCI in a closed-loop BCI simulator with nine human subjects performing a typing task. We demonstrate that our AI-BCI achieves: (1) categorically higher information communication rates, (2) quicker ballistic movements between targets, (3) improved precision control to 'dial in' on targets, and (4) more efficient movement trajectories. We further show that our AI-BCI increases performance across a wide control quality spectrum from poor to proficient control.This AI-BCI architecture, by increasing BCI performance across all key metrics evaluated, may increase the clinical viability of BCI systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1741-2552/abfaaaDOI Listing
May 2021

Embedding consumer and community involvement within an established research centre: moving from general recommendations to an actionable framework.

Res Involv Engagem 2020 27;6:64. Epub 2020 Oct 27.

Department of Surgery, The University of Melbourne, St Vincent's Hospital Melbourne, Melbourne, Australia.

Plain English Summary: Involving consumers and community members in the research process is an important step towards developing and delivering effective, person-centered health care. The National Health and Medical Research Council have provided recommendations for involving consumers and community members in research; however, definitive actions to implement these are not well defined.To address this, an established research centre in Melbourne, Australia, has developed a consumer and community involvement framework to incorporate the national recommendations into their research program. This paper describes the framework the research centre has employed, in the hope that other researchers can adapt this approach and learnings to their own research practices.The framework described in this paper aims to foster partnerships between consumers, community members and researchers, and in doing so, encourages consumers to be actively involved in research to help improve future outcomes for those living with musculoskeletal conditions. Simultaneously, the framework encourages researchers to value the consumer voice in their research to ensure they yield meaningful research outcomes for those living with musculoskeletal conditions.

Abstract: The value of involving consumers and community members in every stage of the research process is gaining recognition as an important consideration in the wider research landscape. The National Health and Medical Research Council (NHMRC) has provided general recommendations for involving consumers and community members in research, although the translation of these recommendations into tangible actions has not yet been well defined. In light of these recommendations, many research institutions are now seeking to incorporate the voices of consumers and community members in their research practices.The consumer and community involvement framework described in this paper incorporates the NHMRC's recommendations to produce a four-tiered model where consumer participants nominate their level of involvement depending on their research interests and preferred level of commitment. In ascending order, the tiers are: Consumer Subscriber, Document Reviewer, Research Buddy and Consumer Advocate.The success of this framework depends upon the implementation of effective governance and access to appropriate infrastructure. A Consumer and Community Advisory Group and a designated Consumer and Community Liaison Officer will take responsibility for ensuring appropriate interactions between consumers, researchers, and the research center's executive team. The framework aims to apply suitable support structures in place to manage expectations and minimize barriers to effective involvement, whilst ensuring that consumer contributions are appropriately valued and incorporated in the research.Involving consumers and community members in the research process is an important step towards developing and delivering effective, person-centered health care. While consumer and community involvement offer researchers invaluable perspectives on their research program, it provides an opportunity for consumers and community members to be actively involved in health research and improve the health and wellbeing for those living with health conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40900-020-00241-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592531PMC
October 2020

Entropic Trapping of DNA with a Nanofiltered Nanopore.

ACS Appl Nano Mater 2019 Aug 19;2(8):4773-4781. Epub 2019 Jun 19.

Department of Physics, University of Ottawa, Ottawa, ON, Canada.

Elucidating the kinetics of DNA passage through a solid-state nanopore is a fertile field of research, and mechanisms for controlling capture, passage, and trapping of biopolymers are likely to find numerous technological applications. Here we present a nanofiltered nanopore device, which forms an entropic cage for DNA following first passage through the nanopore, trapping the translocated DNA and permitting recapture for subsequent reanalysis and investigation of kinetics of passage under confinement. We characterize the trapping properties of this nanodevice by driving individual DNA polymers into the nanoscale gap separating the nanofilter and the pore, forming an entropic cage similar to a "two pores in series" device, leaving polymers to diffuse in the cage for various time lengths, and attempting to recapture the same molecule. We show that the cage results in effectively permanent trapping when the radius of gyration of the target polymer is significantly larger than the radii of the pores in the nanofilter. We also compare translocation dynamics as a function of translocation direction in order to study the effects of confinement on DNA just prior to translocation, providing further insight into the nanopore translocation process. This nanofiltered nanopore device realizes simple fabrication of a femtoliter nanoreactor in which to study fundamental biophysics and biomolecular reactions on the single-molecule level. The device provides an electrically-permeable single-molecule trap with a higher entropic barrier to escape than previous attempts to fabricate similar structures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsanm.9b00606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310961PMC
August 2019

Prelabor short-term variability in fetal heart rate by computerized cardiotocogram and maternal fetal doppler indices for the prediction of labor outcomes.

J Matern Fetal Neonatal Med 2020 Apr 14:1-10. Epub 2020 Apr 14.

Department of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR.

To investigate (i) the association between pre-labor maternal-fetal Dopplers and fetal heart rate short-term variability (FHR STV) with arterial cord blood pH and (ii) the potential value of pre-labor maternal-fetal Dopplers, FHR STV and Dawes-Redman criteria in predicting composite neonatal morbidity at term in a cohort of unselected women. A prospective study in 218 women with term singleton pregnancy in latent phase of labor or due to undergo induction of labor. Data on maternal characteristics, maternal-fetal Dopplers indices and computerized cardiotocography (CTG) findings of FHR STV and Dawes-Redman criteria were collected. Pearson correlation analysis was used to determine the relationship between maternal-fetal Dopplers and FHR STV and arterial cord blood pH. Logistic regression analysis was used to determine which factors amongst maternal characteristics, labor onset, indication of labor induction, estimated fetal weight (EFW), maternal-fetal Dopplers, FHR STV and Dawes-Redman criteria were significant predictors of composite neonatal morbidity and arterial cord blood pH less than 7.2. Of the 218 cases, 12 (5.5%) women were delivered by emergency operative delivery for pathological CTG, and 42 babies (19.3%) had composite neonatal morbidities. Arterial cord blood pH was not associated with maternal-fetal Doppler indices and FHR STV, but rather it was associated with maternal age and body mass index. The composite neonatal morbidity and arterial cord blood pH less than 7.2 were not significantly associated with maternal characteristics, labor onset, indication of labor induction, pre-labor assessment of EFW, maternal-fetal Doppler indices, FHR STV and Dawes-Redman criteria by computerized CTG. In unselected women in latent phase of labor or undergoing induction of labor at term, admission maternal-fetal Doppler indices, FHR STV and Dawes-Redman criteria are not predictive of composite neonatal morbidity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2020.1752657DOI Listing
April 2020

Engaging patients to access the community pharmacy medicine review service after discharge from hospital: a cross-sectional study in England.

Int J Clin Pharm 2019 Aug 9;41(4):1110-1117. Epub 2019 May 9.

Medway School of Pharmacy, Universities of Kent and Greenwich at Medway, Chatham Maritime, ME4 4TB, UK.

Background The post-discharge Medicines-Use-Review (dMUR) is a commissioned service in England and Wales whereby community pharmacists facilitate patients' understanding of their medicines and resolve any medicine-related problems. This service is poorly utilised. Objective To explore the impact of raising hospital patients' awareness of dMURs on their uptake. Setting Hospital in South East England. Method Patients on medical wards with at least one change (medicine, or dose regimen) to their admission medicines were provided with standardized written and verbal information about the service. Participants were responsible for their own medicines and anticipated that they would be discharged home. Structured telephone interviews conducted 4 weeks after discharge explored any medicine-related issues experienced, and reasons for engaging, or not, with the dMUR service. Responses to closed questions were analysed using descriptive statistics. Responses to open questions were analysed thematically. Ethics approval was obtained. Main outcome measure Proportion of patients who received a dMUR and their motivations or barriers to accessing the service. Results Hundred patients were recruited and 84 interviewed. Their mean (SD) age was 73 (11) years. They were taking a median (range) of 9 (2-19) medicines. 67% (56/84) remembered receiving information about dMURs. Nine (11%) had attempted to make an appointment although four had not received the service because the pharmacist was unavailable. Most (88%) were not planning to access the service. The most common reason given was poor morbidity or mobility (13/31, 42%). Conclusion The use of written and verbal information to encourage patients to use the dMUR service had minimal impact.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11096-019-00838-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677689PMC
August 2019

Role of capillary pericytes in the integration of spontaneous Ca transients in the suburothelial microvasculature in situ of the mouse bladder.

J Physiol 2018 08 24;596(16):3531-3552. Epub 2018 Jun 24.

Department of Cell Physiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.

Key Points: In the bladder suburothelial microvasculature, pericytes in different microvascular segments develop spontaneous Ca transients with or without associated constrictions. Spontaneous Ca transients in pericytes of all microvascular segments primarily rely on the cycles of Ca uptake and release by the sarco- and endoplasmic reticulum. The synchrony of spontaneous Ca transients in capillary pericytes exclusively relies on the spread of depolarizations resulting from the opening of Ca -activated chloride channels (CaCCs) via gap junctions. CaCC-dependent depolarizations further activate L-type voltage-dependent Ca channels as required for the synchrony of Ca transients in pericytes of pre-capillary arterioles, post-capillary venules and venules. Capillary pericytes may drive spontaneous Ca transients in pericytes within the suburothelial microvascular network by sending CaCC-dependent depolarizations via gap junctions.

Abstract: Mural cells in the microvasculature of visceral organs develop spontaneous Ca transients. However, the mechanisms underlying the integration of these Ca transients within a microvascular unit remain to be clarified. In the present study, the origin of spontaneous Ca transients and their propagation in the bladder suburothelial microvasculature were explored. Cal-520 fluorescence Ca imaging and immunohistochemistry were carried out on mural cells using mice expressing red fluorescent protein (DsRed) under control of the NG2 promotor. NG2(+) pericytes in both pre-capillary arterioles (PCAs) and capillaries developed synchronous spontaneous Ca transients. By contrast, although NG2-DsRed also labelled arteriolar smooth muscle cells, these cells remained quiescent. Both NG2(+) pericytes in post-capillary venules (PCVs) and NG2(-) venular pericytes exhibited propagated Ca transients. L-type voltage-dependent Ca channel (LVDCC) blockade with nifedipine prevented Ca transients or disrupted their synchrony in PCA, PCV and venular pericytes without dis-synchronizing Ca transients in capillary pericytes. Blockade of gap junctions with carbenoxolone or Ca -activated chloride channels (CaCCs) with 4,4'-diisothiocyanato-2,2'-stilbenedisulphonic acid disodium salt prevented Ca transients in PCA and venular pericytes and disrupted the synchrony of Ca transients in capillary and PCV pericytes. Spontaneous Ca transients in pericytes of all microvascular segments were abolished or suppressed by cyclopiazonic acid, caffeine or tetracaine. The synchrony of Ca transients in capillary pericytes arising from spontaneous Ca release from the sarco- and endoplasmic reticulum appears to rely exclusively on CaCC activation, whereas subsequent LVDCC activation is required for the synchrony of Ca transients in pericytes of other microvascular segments. Capillary pericytes may drive spontaneous activity in the suburothelial microvascular unit to facilitate capillary perfusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1113/JP275845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092302PMC
August 2018

Prevalence and sociodemographic correlates of routine breast cancer screening practices among migrant-Australian women.

Aust N Z J Public Health 2018 Feb 13;42(1):98-103. Epub 2017 Dec 13.

Discipline of Physiotherapy, Faculty of Health Sciences, The University of Sydney, New South Wales.

Objective: To evaluate breast cancer screening (BCS) practice and explore the relationship between sociodemographic factors and breast awareness (BA), clinical breast examination (CBE) and mammography in migrant-Australian women.

Method: Secondary analysis was performed on the pooled sample (n=1,744) from five cross-sectional studies of BCS rates among immigrant-Australian women, and the associated sociodemographic factors.

Results: Only 19% of women participated in routine BA, 27.4% of women in the target group of >40 year presented for an annual CBE, and 60.6% of women in the target group of 50-74 years received a biennial mammogram. Associated sociodemographic factors differed by modality except for length of Australian residency. In multivariable analysis, age, length of Australian residency, marital status, and employment status accounted for more than 50% of the variance in regular BA and CBE.

Conclusion: These findings indicate suboptimal BCS rates persist among migrant-Australian women, and suggest the importance of certain sociodemographic factors in BCS practice. Implications for public health: Further education is required for BA and CBE practice in immigrant-Australian women, especially for those who have resided in Australia less than 12 years without a partner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1753-6405.12752DOI Listing
February 2018

Changes in Personal Relationships During Residency and Their Effects on Resident Wellness: A Qualitative Study.

Acad Med 2017 11;92(11):1601-1606

M. Law is associate professor of family medicine and director of Foundations, MD Program, University of Toronto, as well as director of medical education, Michael Garron Hospital, Toronto, Ontario, Canada. M. Lam is a family physician, Hamilton, Ontario, Canada. D. Wu is a family physician, Toronto, Ontario, Canada. P. Veinot is an independent research consultant, Toronto, Ontario, Canada. M. Mylopoulos is assistant professor, Faculty of Medicine, and scientist, Wilson Centre, University of Toronto, Toronto, Ontario, Canada.

Purpose: Residency poses challenges for residents' personal relationships. Research suggests residents rely on family and friends for support during their training. The authors explored the impact of residency demands on residents' personal relationships and the effects changes in those relationships could have on their wellness.

Method: The authors used a constructivist grounded theory approach. In 2012-2014, they conducted semistructured interviews with a purposive and theoretical sample of 16 Canadian residents from various specialties and training levels. Data analysis occurred concurrently with data collection, allowing authors to use a constant comparative approach to explore emergent themes. Transcripts were coded; codes were organized into categories and then themes to develop a substantive theory.

Results: Residents perceived their relationships to be influenced by their evolving professional identity: Although personal relationships were important, being a doctor superseded them. Participants suggested they were forced to adapt their personal relationships, which resulted in the evolution of a hierarchy of relationships that was reinforced by the work-life imbalance imposed by their training. This poor work-life balance seemed to result in relationship issues and diminish residents' wellness. Participants applied coping mechanisms to manage the conflict arising from the adaptation and protect their relationships. To minimize the effects of identity dissonance, some gravitated toward relationships with others who shared their professional identity or sought social comparison as affirmation.

Conclusions: Erosion of personal relationships could affect resident wellness and lead to burnout. Educators must consider how educational programs impact relationships and the subsequent effects on resident wellness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ACM.0000000000001711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662155PMC
November 2017

Determining the Prevalence of and Risk Factors for Depressive Symptoms among Adults in Nepal.

Int J Noncommun Dis 2017 ;2(1):18-26

University of Washington, Department of Global Health.

Context: Nepal is currently experiencing a rapid growth in non-communicable diseases (NCDs). Depression has previously been associated with NCDs in South Asia; however, data regarding its prevalence and risk factors is lacking in Nepal.

Aims: This study aims to describe the prevalence of and risk factors for depressive symptoms in a suburban population of adults within Nepal.

Setting And Design: We conducted a cross-sectional analysis of baseline data collected from participants enrolled in the Dhulikhel Heart Study (DHS), a population-based, longitudinal cohort study investigating cardiovascular risk factors in Dhulikhel, a suburban town outside Kathmandu.

Subjects And Methods: Baseline questionnaire data from 1,073 adults age 18 years and older included the Center for Epidemiologic Studies Depression Scale (CESD). A score of 16 or greater on the CESD has been shown to indicate major depressive symptomatology.

Statistical Analysis: Using STATA 13 we conducted Pearson's chi-squared tests and multiple logistic regressions to examine associations between the binary CESD score and gender, age, education, marital status, body mass index (BMI), physical activity, and hypertensive status.

Results: The mean CESD score in the sample was 11.7 (SD: 5.3), with 21.3% scoring 16 or greater. Age over 60 and lack of formal education were associated with increased risk of depressive symptoms. Being physically active was associated with decreased risk of depressive symptoms.

Conclusions: The estimated prevalence of depression among adults in Dhulikhel was 21.3%. Significant risk factors for increased depressive symptoms included lack of formal education, age over 60, and physical inactivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/jncd.jncd_34_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298440PMC
January 2017

Electrical properties of purinergic transmission in smooth muscle of the guinea-pig prostate.

Auton Neurosci 2016 Jan 25;194:8-16. Epub 2015 Nov 25.

Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Kawasumi-1, Mizuho-ku, Nagoya 467-8601, Japan.

Prostatic smooth muscle develops spontaneous myogenic tone which is modulated by autonomic neuromuscular transmission. This study aimed to investigate the role of purinergic transmission in regulating electrical activity of prostate smooth muscle and whether its contribution may be altered with age. Intracellular recordings were simultaneously made with isometric tension recordings in smooth muscle preparations of the guinea-pig prostate. Immunostaining for P2X1 receptors on whole mount preparations was also performed. In prostate preparations which generated spontaneous slow waves, electrical field stimulation (EFS)-evoked excitatory junction potentials (EJPs) which were abolished by guanethidine (10 μM), α-β-methylene ATP (10 μM) or pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (PPADS, 10 μM) but not phentolamine (1 μM). Consistently, immunostaining revealed the expression of P2X1 receptors on prostatic smooth muscle. EJPs themselves did not cause contractions, but EJPs could sum to trigger a slow wave and associated contraction. Yohimbine (1 μM) and 3,7-dimethyl-1-propargylxanthine (DMPX, 10 μM) but not propranolol (1 μM) potentiated EJPs. Although properties of EJPs were not different between young and aging guinea-pig prostates, ectoATPase inhibitor ARL 67156 (100 μM) augmented EJP amplitudes by 64.2 ± 29.6% in aging animals, compared to 22.1 ± 19.9% in young animals. These results suggest that ATP released from sympathetic nerves acts on P2X1 purinoceptors located on prostate smooth muscle to evoke EJPs, while pre-junctional α2-adrenergic and adenosine A2 receptors may play a role in preventing excessive transmitter release. Age-related up-regulation of enzymatic ATP breakdown may be a compensatory mechanism for the enhanced purinergic transmission which would cause hypercontractility arising from increased ATP release in older animals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.autneu.2015.11.003DOI Listing
January 2016

Voltage dependence of slow wave frequency in the guinea pig prostate.

J Urol 2014 Oct 15;192(4):1286-92. Epub 2014 Mar 15.

Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. Electronic address:

Purpose: Spontaneous phasic contractions of the guinea pig prostate stroma result from the generation of slow waves that appear to primarily rely on spontaneous Ca(2+) release from the endoplasmic/sarcoplasmic reticulum and subsequent opening of Ca(2+) activated chloride channels. We investigated voltage dependent mechanisms in the regulation of slow wave frequency.

Materials And Methods: Changes in membrane potential were recorded using conventional intracellular recording techniques while simultaneously measuring the isometric tension of guinea pig prostate lobes. Fluorescence immunohistochemistry was done to determine the cellular composition of the prostate stroma.

Results: Depolarization induced by high K(+) solution, K(+) free solution or outward current injection was associated with increased slow wave frequency. In contrast, hyperpolarization induced by the re-addition of K(+), adenosine triphosphate sensitive K(+) channel openers or inward current injection prevented slow wave generation. K(+) channel openers induced hyperpolarization and the cessation of slow waves was reversed by glibenclamide (10 μM). Nifedipine (1 to 10 μM) shortened the duration of slow waves and pacemaker potentials but often failed to prevent their generation and associated contractions. Subsequently Ni(2+) (100 μM) or mibefradil (1 μM) largely suppressed slow waves and abolished residual contractions. Immunohistochemistry revealed small interconnected smooth muscle bundles as well as vimentin positive interstitial cells but failed to show a network of Kit positive interstitial cells.

Conclusions: Prostate slow wave frequency is voltage dependent due to the significant contribution of L-type and T-type Ca(2+) channels. Prostate slow waves may arise from cooperation between spontaneous Ca(2+) release from internal stores and plasmalemmal voltage dependent Ca(2+) channels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.juro.2014.03.034DOI Listing
October 2014

Tamsulosin modulates, but does not abolish the spontaneous activity in the guinea pig prostate gland.

Neurourol Urodyn 2015 Jun 16;34(5):482-8. Epub 2014 Jan 16.

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria 3052, Australia.

Aims: To examine the effects of the α1A -adrenoceptor antagonist, tamsulosin, on spontaneous contractile and electrical activity in the guinea-pig prostate gland.

Methods: The effects of tamsulosin (0.1 and 0.3 nM) were investigated in adult and ageing male guinea pig prostate glands using conventional tension recording and electrophysiological intracellular microelectrode recording techniques.

Results: Tamsulosin reduced spontaneous activity, and had different age-dependent effects on adult and ageing guinea pigs at different concentrations. 0.1 nM tamsulosin caused a significantly greater reduction of spontaneous contractile and electrical activity in ageing guinea pigs in comparison to adult guinea pigs. In contrast, 0.3 nM tamsulosin had a significantly greater reduction of spontaneous contractile and electrical activity in adult guinea pigs in comparison to ageing guinea pigs.

Conclusions: This study demonstrates that tamsulosin can modulate spontaneous myogenic stromal contractility and the underlying spontaneous electrical activity; tamsulosin does not block spontaneous activity. This reduction in spontaneous activity suggests that downstream cellular mechanisms underlying smooth muscle tone are being targeted, and these may represent novel therapeutic targets to better treat benign prostatic hyperplasia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nau.22557DOI Listing
June 2015

Identification of barriers to the prevention and treatment of heat-related illness in Latino farmworkers using activity-oriented, participatory rural appraisal focus group methods.

BMC Public Health 2013 Oct 24;13:1004. Epub 2013 Oct 24.

School of Medicine, University of Washington, Seattle, WA, USA.

Background: Heat-related illness (HRI) is an important cause of non-fatal illness and death in farmworkers. We sought to identify potential barriers to HRI prevention and treatment in Latino farmworkers.

Methods: We conducted three semi-structured focus group discussions with 35 Latino farmworkers in the Central Washington, USA area using participatory rural appraisal techniques. Interviews were audio taped and transcribed in Spanish. Three researchers reviewed and coded transcripts and field notes, and investigator triangulation was used to identify relevant themes and quotes.

Results: Although the majority of participants in our study reported never receiving formal HRI training, most participants were aware that extreme heat can cause illness and were able to accurately describe HRI symptoms, risk factors, and certain prevention strategies. Four main observations regarding farmworkers' HRI-relevant beliefs and attitudes were identified: 1) farmworkers subscribe to varying degrees to the belief that cooling treatments should be avoided after heat exposure, with some believing that such treatments should be avoided after heat exposure, and others encouraging the use of such treatments; 2) the desire to lose weight may be reflected in behaviors that promote increased sweating; 3) highly caffeinated energy drinks are preferred to increase work efficiency and maintain alertness; and 4) the location of drinking water at work (e.g. next to restrooms) and whether water is clean, but not necessarily chemically-treated, are important considerations in deciding whether to drink the water provided at worksites.

Conclusions: We identified potential barriers to HRI prevention and treatment related to hydration, certain HRI treatments, clothing use, and the desire to lose weight among Latino farmworkers. Strategies to address potential barriers to HRI prevention and treatment in this population may include engineering, administrative, and health education and health promotion strategies at individual, workplace, community, and societal levels. Although farmworkers in our study were able to describe HRI risk factors, reported practices were not necessarily consistent with reported knowledge. Further study of potential knowledge-behavior gaps may uncover opportunities for additional HRI prevention strategies. Farmworkers and employers should be included in the development and evaluation of interventions to prevent HRI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2458-13-1004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015616PMC
October 2013

Effects of imatinib mesylate on the spontaneous activity generated by the guinea-pig prostate.

BJU Int 2013 Aug;112(4):E398-405

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Australia.

Unlabelled: What's known on the subject? and what does the study add?: Several studies have examined the functional role of tyrosine kinase receptors in the generation of spontaneous activity in various segments of the gastrointestinal and urogenital tracts through the application of its inhibitor, imatinib mesylate (Glivec®), but results are fairly inconsistent. This is the first study detailing the effects of imatinib mesylate on the spontaneous activity in the young and ageing prostate gland. As spontaneous electrical activity underlies the spontaneous rhythmic prostatic contractions that occur at rest, elucidating the mechanisms involved in the regulation of the spontaneous electrical activity and the resultant phasic contractions could conceivably lead to the identification of better targets and the development of more specific therapeutic agents to treat prostate conditions.

Objective: To investigate the effect of imatinib mesylate, a tyrosine kinase receptor inhibitor, in the generation of spontaneous electrical and contractile activity in the young and ageing guinea-pig prostate.

Materials And Methods: Standard tension and intracellular recording were used to measure spontaneous contractions and slow waves, respectively from the guinea-pig prostate at varying concentrations of imatinib mesylate (1-50 μm).

Results: Imatinib mesylate (1-10 μm), did not significantly affect slow waves recorded in the prostate of both age groups but at 50 μm, the amplitude of slow waves from the ageing guinea-pig prostate was significantly reduced (P < 0.05, n = 5). In contrast, the amplitude of contractions across all concentrations in the young guinea-pig prostate was reduced to between 35% and 41% of control, while the frequency was reduced to 15.7% at 1 μm (n = 7), 49.8% at 5 μm (n = 10), 46.2% at 10 μm (n = 7) and 53.1% at 50 μm (n = 5). Similarly, imatinib mesylate attenuated the amplitude and slowed the frequency of contractions in ageing guinea-pigs to 5.15% and 3.3% at 1 μm (n = 6); 21.1% and 20.8% at 5 μm (n = 8); 58.4% and 8.8% at 10 μm (n = 11); 72.7% and 60% at 50 μm (n = 5).

Conclusions: A significant reduction in contractions but persistence of slow waves suggests imatinib mesylate may affect the smooth muscle contractile mechanism. Imatinib mesylate also significantly reduced contractions in the prostates of younger guinea pigs more than older ones, which is consistent with the notion that the younger guinea-pig prostate is more reliant on the tyrosine-dependent pacemaker ability of interstitial cells of Cajal-like prostatic interstitial cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1464-410X.2012.11660.xDOI Listing
August 2013

Involvement of Rho-kinase signaling pathways in nerve evoked and spontaneous contractions of the Guinea pig prostate.

J Urol 2013 Mar 8;189(3):1147-54. Epub 2012 Oct 8.

Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.

Purpose: Men with benign prostatic hyperplasia commonly experience irritative lower urinary tract symptoms, which are due at least in part to enhanced prostatic smooth muscle tone. To provide some insight into the changes that occur in prostatic contractility with age, we examined the contribution of rho-kinase dependent Ca(2+) sensitization in neurogenic and spontaneous contractions of young and aging guinea pig prostates.

Materials And Methods: We used conventional tension recording and electrophysiological intracellular microelectrode recording techniques.

Results: The Rho-kinase inhibitor Y-27632 (10 and 100 μM) significantly inhibited electrical field stimulated evoked (neurogenic) contractions in the guinea pig prostate in a dose dependent manner. In addition, Y-27632 (1 and 10 μM) similarly suppressed tetrodotoxin insensitive spontaneous contractions in dose dependent fashion. While Y-27632 at 10 μM decreased spontaneous contractions of young and aging guinea pig prostates, as evidenced by a significant decrease in the AUC, there was no significant difference in the degree of inhibition between the 2 age groups. In contrast to contractile activity, Y-27632 did not affect the generation or modulation of spontaneous slow wave electrical activity, which underlies spontaneous contractions.

Conclusions: There are strong indicators that Rho-kinase signaling pathways have a significant role in prostatic smooth muscle contractility, most likely independent of cytosolic Ca(2+) levels. Features of the rho-kinase pathway may well represent alternative, novel future therapeutic targets to reduce prostatic contractility, thereby alleviating the lower urinary tract symptoms arising from benign prostatic hyperplasia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.juro.2012.08.220DOI Listing
March 2013

Spontaneous Ca2+ signaling of interstitial cells in the guinea pig prostate.

J Urol 2011 Dec 21;186(6):2478-86. Epub 2011 Oct 21.

Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia.

Purpose: We investigated whether prostate interstitial cells generate spontaneous Ca(2+) oscillation, a proposed mechanism underlying pacemaker potentials to drive spontaneous activity in stromal smooth muscle cells.

Materials And Methods: Intracellular free Ca(2+) in portions of guinea pig prostate and freshly isolated, single prostate interstitial cells were visualized using fluo-4 Ca(2+) fluorescence. Spontaneous electrical activity was recorded in situ with intracellular microelectrodes.

Results: In whole tissue preparations spontaneous Ca(2+) flashes firing synchronously across all smooth muscle cells within the field of view resulted in muscle wall contractions. Nonpropagating Ca(2+) waves were also recorded in individual smooth muscle cells. Nifedipine (Sigma®) (1 μM) largely decreased or abolished these Ca(2+) flashes and suppressed slow wave discharge upon blockade of their superimposed action potentials. Isolated prostate interstitial cells were readily distinguished from smooth muscle cells by their spiky processes and lack of contraction during intracellular Ca(2+) increases. Prostate interstitial cells generated spontaneous Ca(2+) transients in the form of whole cell flashes, intracellular Ca(2+) waves or localized Ca(2+) sparks. All 3 Ca(2+) signals were abolished by nicardipine (1 μM), cyclopiazonic acid (10 μM), caffeine (Sigma) (10 mM) or extracellular Ca(2+) removal.

Conclusions: Prostate interstitial cells generate spontaneous Ca(2+) transients that occur at a frequency comparable to Ca(2+) flashes in situ or slow waves relying on functional internal Ca(2+) stores. However, unlike other interstitial cells in the urinary tract, Ca(2+) influx through L-type Ca(2+) channels is fundamental to Ca(2+) transient firings in prostate interstitial cells. Thus, it is not possible to conclude that prostate interstitial cells are responsible for pacemaker potential generation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.juro.2011.07.082DOI Listing
December 2011

Closed claims' analysis.

Best Pract Res Clin Anaesthesiol 2011 Jun;25(2):263-76

Department of Anesthesiology & Pain Medicine, Box 356540, University of Washington, Seattle, WA 98195-6540, USA.

The American Society of Anesthesiologists (ASA) Closed Claims database was started in 1985 to study anaesthesia injuries to improve patient safety, now containing 8954 claims with 5230 claims since 1990. Over the decades, claims for surgical anaesthesia decreased, while claims for acute and chronic pain management increased. In the 2000s, chronic pain management involved 18%, acute pain management 9% and obstetrical anaesthesia formed 8% of claims. Surgical anaesthesia claims with monitored anaesthesia care (MAC) increased in the 2000s to 10% of claims, while regional anaesthesia involved 19%. The most common complications were death (26%), nerve injury (22%) and permanent brain damage (9%). The most common damaging events due to anaesthesia in claims were regional-block-related (20%), respiratory (17%), cardiovascular (13%) and equipment-related events (10%). This review examines recent findings and clinical implications for injuries in management of the difficult airway, MAC, non-operating room locations, obstetric anaesthesia and chronic pain management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bpa.2011.02.007DOI Listing
June 2011

Extracellular Ca(2+) entry and mobilization of inositol trisphosphate-dependent Ca(2+) stores modulate histamine and electrical field stimulation induced contractions of the guinea-pig prostate.

Pharmacol Res 2011 Sep 25;64(3):235-41. Epub 2011 Apr 25.

Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.

This investigation aimed to examine the source of Ca(2+) mobilization that leads to the contractile response to either exogenously added histamine (1 μM-1mM) or electrical field stimulation (10Hz, 0.5ms, 60V). Removal of extracellular Ca(2+) by removal of Ca(2+) from the bathing medium reduced histamine (1mM) induced responses by 34% and responses induced by electrical field stimulation by 94%. Similarly, blockade of L-type Ca(2+) channels by nifedipine (1 μM) reduced histamine (1mM) induced responses by 43% and responses induced by electrical field stimulation by 77%. Application of cyclopiazonic acid (CPA) (10 μM) to inhibit Ca(2+) reuptake to the sarcoplasmic reticulum enhanced both histamine-induced and electrical field stimulation induced responses to a small degree, while the addition of the inosotol triphosphate (IP(3)) receptor antagonist, 2-aminophenoxyethane borane (2-APB) (100 μM) inhibited histamine induced responses by 70% and electrical field stimulation induced responses by 57%. Ryanodine (1 μM) did not affect contractile responses to either histamine or electrical field stimulation, either in the absence or presence of 2-APB (100 μM). During both histamine and electrical field stimulation induced contractions, prostate smooth muscle generates IP(3) receptor mediated Ca(2+) release in conjunction with Ca(2+) entry from the extracellular environment. Ryanodine receptors on the other hand, appear not to play a role in this physiological mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2011.04.009DOI Listing
September 2011

The effect of early Pseudomonas aeruginosa treatment on lung function in pediatric cystic fibrosis.

Pediatr Pulmonol 2011 Jun 18;46(6):554-8. Epub 2011 Feb 18.

Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.

Objective: Our aim was to assess the effect of treatment of early infection of P. aeruginosa on pulmonary function in pediatric CF patients.

Methods: This was a retrospective cohort study of P. aeruginosa negative CF patients followed at Sick Kids from 1990 to 2007. Early P. aeruginosa infection was defined as the first respiratory culture for P. aeruginosa; patients were included if 5 years of follow-up pulmonary function data were available. Patients were divided into three groups (group 1: never infected, group 2: infected with subsequent clearance, and group 3: chronic infection or still receiving antipseudomonal antibiotics). Hierarchical linear models were used to estimate the effect of P. aeruginosa infection on spirometry. FEV(1) % predicted was the primary outcome.

Results: 116 patients were included. Forty-six (40%) patients remained P. aeruginosa negative throughout the observation period, 29 (25%) patients transiently infected with P. aeruginosa, and 41 (35%) patients were either currently infected or still receiving treatment. Baseline lung function was the same for all groups. Annual decline in FEV(1) % predicted during the study period was not different (-0.6%/year for patients that were never infected and -1.3%/year among patients previously infected).

Conclusions: Lung function was not different between patients with early P. aeruginosa infection and those that never had P. aeruginosa infection. However given the slow rate of FEV(1) decline in the study population, a longer observation period and/or more sensitive outcomes measures may be required to exclude long-term detrimental effects of transient P. aeruginosa infection on lung function in CF patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ppul.21417DOI Listing
June 2011

Monodisperse cobalt ferrite nanomagnets with uniform silica coatings.

Langmuir 2010 Nov 20;26(22):17546-51. Epub 2010 Oct 20.

IBM Almaden Research Center, 650 Harry Road, San Jose, California 95120, United States.

Ferro- and ferrimagnetic nanoparticles are difficult to manipulate in solution as a consequence of the formation of magnetically induced nanoparticle aggregates, which hamper the utility of these particles for applications ranging from data storage to bionanotechnology. Nonmagnetic shells that encapsulate these magnetic particles can reduce the interparticle magnetic interactions and improve the dispersibility of the nanoparticles in solution. A route to create uniform silica shells around individual cobalt ferrite nanoparticles--which uses poly(acrylic acid) to bind to the nanoparticle surface and inhibit nanoparticle aggregation prior to the addition of a silica precursor--was developed. In the absence of the poly(acrylic acid) the cobalt ferrite nanoparticles irreversibly aggregated during the silica shell formation. The thickness of the silica shell around the core-shell nanoparticles could be controlled in order to tune the interparticle magnetic coupling as well as inhibit magnetically induced nanoparticle aggregation. These ferrimagnetic core-silica shell structures form stable dispersion in polar solvents such as EtOH and water, which is critical for enabling technologies that require the assembly or derivatization of ferrimagnetic particles in solution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/la103042qDOI Listing
November 2010

Self-assembled ferrimagnet--polymer composites for magnetic recording media.

Nano Lett 2010 Aug;10(8):3216-21

IBM Almaden Research Center, 650 Harry Road, San Jose, California 95120, USA.

A self-assembled magnetic recording medium was created using colloidal ferrimagnetic building blocks. Monodisperse cobalt ferrite nanoparticles (CoFe(2)O(4)) were synthesized using solution-based methods and then stabilized in solution using the amphiphilic diblock copolymer, poly(acrylic acid)-b-poly(styrene) (PAA-PS). The acid groups of the acrylate block bound the polymer to the nanoparticle surface via multivalent interactions, while the styrene block afforded the magnetic nanoparticle--polymer complex solubility in organic solvents. Moreover, the diblock copolymer improved the colloidal stability of the ferrimagnetic CoFe(2)O(4) nanoparticles by reducing the strong interparticle magnetic interactions, which typically caused the ferrimagnetic nanoparticles to irreversibly aggregate. The nanoparticle--polymer complex was spin-coated onto a silicon substrate to afford self-organized thin film arrays, with the interparticle spacing determined by the molecular weight of the diblock copolymer. The thin film composite was also exposed to an external magnetic field while simultaneously heated above the glass transition temperature of poly(styrene) to allow the nanoparticles to physically rotate to align their easy axes with the direction of the magnetic field. In order to demonstrate that this self-assembled ferrimagnet--polymer composite was suitable as a magnetic recording media, read/write cycles were demonstrated using a contact magnetic tester. This work provides a simple route to synthesizing stabilized ferrimagnetic nanocrystals that are suitable for developing magnetic recording media.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/nl1022749DOI Listing
August 2010

Inositol trisphosphate-dependent Ca stores and mitochondria modulate slow wave activity arising from the smooth muscle cells of the guinea pig prostate gland.

Br J Pharmacol 2009 Apr 25;156(7):1098-106. Epub 2009 Feb 25.

Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria 3052, Australia.

Background And Purpose: Changes in smooth muscle tone of the prostate gland are involved in aetiology of symptomatic prostatic hyperplasia, however the control mechanisms of prostatic smooth muscle are not well understood. Here, we have examined the role of internal Ca(2+) compartments in regulating slow wave activity in the guinea pig prostate.

Experimental Approach: Standard intracellular membrane potential recording techniques were used.

Key Results: The majority (89%) of impaled cells displayed 'slow wave' activity. Cyclopiazonic acid (10 micromol.L(-1)) transiently depolarized (3-9 mV) the membrane potential of the prostatic stroma and transiently increased slow wave frequency. Thereafter, slow wave frequency slowly decreased over 20-30 min. Ryanodine transiently increased slow wave frequency, although after 30 min exposure slow wave frequency and time course returned to near control values. Caffeine (1 mmol.L(-1)) reduced slow wave frequency, accompanied by membrane depolarization of about 8 mV. Blockade of inositol trisphosphate receptor (IP(3)R)-mediated Ca(2+) release with 2-aminoethoxy-diphenylborate (60 micromol.L(-1)) or Xestospongin C (3 micromol.L(-1)) or inhibiting phospholipase C and IP(3) formation using U73122 (5 micromol.L(-1)) or neomycin (1 and 4 mmol.L(-1)) reduced slow wave frequency, amplitude and duration. The mitochondrial uncouplers, p-trifluoromethoxy carbonyl cyanide phenyl hydrazone (1-10 micromol.L(-1)), carbonyl cyanide m-chlorophenylhydrazone (1-3 micromol.L(-1)) or rotenone (10 micromol.L(-1)), depolarized the membrane (8-10 mV) before abolishing electrical activity.

Conclusion And Implications: These results suggest that slow wave activity was dependent on the cyclical release of Ca(2+) from IP(3)-controlled internal stores and mitochondria. This implies that intracellular compartments were essential in the initiation and/or maintenance of the regenerative contractile activity in the guinea pig prostate gland.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1476-5381.2009.00130.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697694PMC
April 2009

Preinjury beta blockers are associated with increased mortality in geriatric trauma patients.

J Trauma 2008 Nov;65(5):1016-20

Division of Trauma/Critical Care, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Introduction: Beta-blockade decreases mortality and morbidity in selected older patient populations undergoing noncardiac general surgery. We hypothesized that preinjury beta blockade would increase mortality in geriatric trauma patients, given beta-blockers inhibit patient's physiologic responses to hypovolemic shock.

Methods: Patients older than 65 years admitted to a level I trauma center were identified by the trauma registry. Medical records were reviewed for demographic and injury information. Preinjury beta blockade was determined by review of nurse and pharmacy admission histories. Logistic regression was used to determine whether there was any correlation between mortality and the use of preinjury beta blockers. Separate models were developed based on the presence or the absence of head injury.

Results: Of the 1,598 patients older than 65 years admitted between 1996 and 2006, 1,479 met inclusion criteria. Primary reason for exclusion was lack of documentation. Two hundred seventy-three patients were taking beta blockers before their trauma, and 14.7% died before discharge. Mortality in patients not taking beta blockers was 13.4%. Mortality in patients with head injury was 25.9%, significantly associated with warfarin use (OR 2.5, 95% CI 1.3-4.8). In patients without head injury, preinjury beta blockade had a significant association with mortality (OR 2.1, 95% CI 1.1-4.3).

Conclusions: Many factors associated with mortality in elderly trauma patients are similar to the younger patient population. Unique to this population are increased comorbidities and use of prescription medications. Beta blockers, one of these common medications, are associated with increased mortality in the elderly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0b013e3181897eacDOI Listing
November 2008

Quantification of small molecules in plasma with direct analysis in real time tandem mass spectrometry, without sample preparation and liquid chromatographic separation.

Rapid Commun Mass Spectrom 2008 Oct;22(20):3217-24

Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, LLC, 3431 Hillview Ave., Palo Alto, CA 94304, USA.

Recently, a new ion source, Direct Analysis in Real Time (DART), has been introduced which allows direct biological sample introduction into a mass spectrometry (MS) system. The elimination of conventionally required sample preparation and separation by high-performance liquid chromatography (HPLC) prior to MS analysis represents a remarkable opportunity to reduce assay turn-around time, environmental impact and capital/manpower investment. This new technology initially was used in various qualitative applications to directly detect chemicals on solid surfaces, in liquids and gases. In this study, a DART source operating under ambient pressure with ground potential was installed onto a Sciex 4000 tandem mass spectrometer and employed in the sample analysis of plasma based on direct introduction into the DART-MS/MS system. Reasonable precision and accuracy (%CV and %Error, both <10%) were achieved of a significant number of compounds tested in biological fluids. In addition, the limit of detection for 80% of the tested compounds reached 5 ng/mL or lower which is sufficient for pharmaceutical drug discovery support. Finally, experimental conditions that significantly impacted assay performance were investigated with respect to optimization and limitation. Because of its simplicity, fast data acquisition (3-5 s) and low cost, DART has the potential to significantly impact quantitative pharmaceutical analysis in biological matrices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rcm.3726DOI Listing
October 2008

Solvation in electrospray mass spectrometry: effects on the reaction kinetics of fragmentation mediated by ion-neutral complexes.

J Org Chem 2005 Jun;70(13):5111-8

Department of Drug Metabolism and Pharmacokinetics, Roche Pharmaceuticals, 3431 Hillview Avenue, Palo Alto, CA 94304, USA.

In electrospray ionization (ESI) on a triple quadrupole mass spectrometer, benzydamine, a molecule with an N,N-dimethylaminopropoxyl side chain, showed a fragmentation pattern in Q1 scans that is dramatically different from the mass-selected collision-induced dissociation (CID) of its MH(+) ion. The N,N-dimethylimmonium ion, which dominates in Q1 scans at higher energies, is only a minor product in all CID spectra. By using a smaller model molecule, N,N,N',N'-tetramethyl-1,3-propanediamine, with the kinetic energy release measured for the corresponding reaction, we have demonstrated that an ion-neutral complex composed of the N,N-dimethylazetidine cation and a neutral counterpart is involved. When the ion-neutral complex intermediate evolves toward elimination to form the immonium ion, the transition state is stabilized by the neutral species. Solvation of the ion-neutral complex, which obstructs the separation of the two partners by the resulting tighter enclosure, facilitates the elimination by enhancing the stabilization of the transition state. Therefore, the prevalence of the immonium ion in Q1 scans was a result of solvation in the ESI source. In CID reactions, where the decomposing ions are mass-selected and thus solvation does not exist, the immonium ion was a minor product, and the separation of the ion-neutral complex became dominant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jo050398nDOI Listing
June 2005