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1.
J Hosp Infect ; 141: 190-197, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37343768

ABSTRACT

BACKGROUND: Dry surface biofilms (DSBs) have been found abundantly across hospital surfaces within intensive care units and may explain how nosocomial pathogens can remain virulent and persist on surfaces for extended periods. Testing standards governing the performance of disinfectant products employ planktonic models under routine growth conditions, which are known to be less tolerant than their biofilm counterpart. AIM: To evaluate biofilm models cultured under artificial human sweat (AHS), a source of nutrient expected on touch surfaces, to assess the antimicrobial performance of common cleaning agents, including a quaternary ammonium, hydrogen peroxide and active chlorine. METHODS: Five single-species biofilms, using pathogenic bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis, were generated on stainless-steel substrates using a sedimentation protocol under both AHS and nutrient-rich conditions for a direct comparison of phenotypic tolerance. The biofilm models were grown over five days followed by desiccation cycles, before being submerged into the disinfectant solutions for up to 25 min. Epifluorescence (EF) microscopy using LIVE/DEAD™ stain was used to visualize microcolony viability. FINDINGS: The results revealed biofilms cultured under AHS exhibited a greater antimicrobial tolerance and reduced speed of kill for all cleaning agents compared with the routine media; an average reduction of 72.4% vs 96.9%, respectively. EF microscopy revealed traces of viable bacteria across all coupons after disinfection indicating a potential opportunity for regrowth and recontamination. CONCLUSION: The notable difference in biocidal performance between the two growth conditions highlights potential pitfalls within current antimicrobial test standards, and the importance of accurate representation of the microbial challenge.


Subject(s)
Disinfectants , Humans , Disinfectants/pharmacology , Sweat , Disinfection/methods , Biofilms , Hospitals
2.
J Hosp Infect ; 141: 175-183, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37348564

ABSTRACT

BACKGROUND: Dry surface biofilms (DSBs) have been recognized across environmental and equipment surfaces in hospitals and could explain how microbial contamination can survive for an extended period and may play a key role in the transmission of hospital-acquired infections. Despite little being known on how they form and proliferate in clinical settings, DSB models for disinfectant efficacy testing exist. AIM: In this study we develop a novel biofilm model to represent formation within hospitals, by emulating patient to surface interactions. METHODS: The model generates a DSB through the transmission of artificial human sweat (AHS) and clinically relevant pathogens using a synthetic thumb capable of emulating human contact. The DNA, glycoconjugates and protein composition of the model biofilm, along with structural features of the micro-colonies was determined using fluorescent stains visualized by epifluorescence microscopy and compared with published clinical data. RESULTS: Micrographs revealed the heterogeneity of the biofilm across the surface; and reveal protein as the principal component within the matrix, followed by glycoconjugates and DNA. The model repeatably transferred trace amounts of micro-organisms and AHS, every 5 min for up to 120 h on to stainless-steel coupons to generate a biofilm model averaging 1.16 × 103 cfu/cm2 falling within the reported range for clinical DSB (4.20 × 102 to 1.60 × 107 bacteria/cm2). CONCLUSION: Our in vitro DSB model exhibits many phenotypical characteristics and traits to those reported in situ. The model highlights key features often overlooked and the potential for downstream applications such as antibiofilm claims using more realistic microbial challenges.


Subject(s)
Acinetobacter baumannii , Humans , Biofilms , Delivery of Health Care , DNA , Glycoconjugates
3.
J Hosp Infect ; 131: 203-212, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36343745

ABSTRACT

Hospital surfaces contaminated with microbial soiling, such as dry surface biofilms (DSBs), can act as a reservoir for pathogenic micro-organisms, and inhibit their detection and removal during routine cleaning. Studies have recognized that such increases in bioburden can hinder the impact of disinfectants and mask the detection of potential pathogens. Cleanliness within healthcare settings is often determined through routine culture-based analysis, whereby surfaces that exhibit >2.5 colony-forming units (CFU) per cm2 pose a risk to patient health; therefore, any underestimation could have detrimental effects. This study quantified microbial growth on high-touch surfaces in four hospitals in England over 19 months. This was achieved using environmental swabs to sample a variety of surfaces within close proximity of the patient, and plating these on to non-specific low nutrient detection agar. The presence of DSBs on surfaces physically removed from the environment was confirmed using real-time imaging through episcopic differential interference contrast microscopy combined with epifluorescence. Approximately two-thirds of surfaces tested exceeded the limit for cleanliness (median 2230 CFU/cm2), whilst 83% of surfaces imaged with BacLight LIVE/DEAD staining confirmed traces of biofilm. Differences in infection control methods, such as choice of surface disinfectants and cleaning personnel, were not reflected in the microbial variation observed and resulting risk to patients. This highlights a potential limitation in the effectiveness of the current standards for all hospital cleaning, and further development using representative clinical data is required to overcome this limitation.


Subject(s)
Cross Infection , Disinfectants , Microbiota , Humans , State Medicine , Cross Infection/prevention & control , Hospitals , Disinfectants/pharmacology , Disinfection/methods
4.
BMC Public Health ; 22(1): 673, 2022 04 07.
Article in English | MEDLINE | ID: mdl-35392866

ABSTRACT

BACKGROUND: Health promotion for the management of risk factors for non-communicable diseases (NCDs) is an integral part of standard care in South Africa. Most persons presenting with NCDs utilise public primary health care centres for disease management. This mixed-methods study aimed at expanding current understanding of the the influence of standard clinic care (usual care) on perceptions and knowledge of risk factors for NCDs and physical activity (PA) among persons from a low-resourced community. Qualitatively the perceptions of women from a low-resourced community about risk factors for NCDs and PA were explored throughout 24-weeks of standard clinic care. Parallel quantitative data was collected to describe changes in risk factors for NCDs and trends in self-reported knowledge about risk factors of NCDs and PA. METHOD: A convergent-parallel mixed-methods research design was used. The study was carried out in a public primary health care setting, in the North West Province, South Africa. From a convenience sample of 100 participants, 77 African women aged between 34 and 79 years were recruited for the study. Data were collected at three time-points including baseline, 12 weeks, and 24 weeks of a standard clinic care health-promotion programme. The qualitative data was collected during focus group discussions, and the quantitative data included questionnaires on knowledge of physical activity and risk factors for NCDs as well as anthropometric and biological measurements. Qualitative and quantitative data were analysed independently for each phase and then consolidated for interpretation. All data was collected in the same setting. RESULTS: Participants' initial understanding and perceptions of NCD risk factors were poor. Qualitative findings showed that participants knew little about the specific physical activity they could engage in and the role of PA in NCD management. Participants preferred low-intensity activities. Heart-disease knowledge improved significantly at 12 weeks intervention compared to baseline MD = -3.655, p < 0.001. There were improvements in PA knowledge at 12 weeks from baseline MD = -0.625 p = 0.02. There were significant weight (MD = 1.420, p = 0.002) and waist circumference reductions (MD = 0.621, p = 0.02) from baseline to 24 weeks. CONCLUSION: Standard clinic care improved knowledge of physical activity and risk factors for NCDs, but perceptions of risk factors for NCDs and PA were unchanged. This study offers insight into the perceptions held by women from a low-resource setting and how future interventions to manage and prevent NCDs should be structured. TRIAL REGISTRATION: PACTR201609001771813 .


Subject(s)
Noncommunicable Diseases , Adult , Aged , Exercise , Female , Focus Groups , Health Promotion , Humans , Middle Aged , Noncommunicable Diseases/prevention & control , Research Design
5.
Vet Surg ; 48(1): 35-41, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30378125

ABSTRACT

OBJECTIVE: To compare the use of stainless steel staples with absorbable staples for closure of skin incisions in dogs undergoing tibial plateau leveling osteotomy (TPLO). STUDY DESIGN: Prospective study. SAMPLE POPULATION: Client-owned dogs (n = 80). METHODS: With client consent, dogs were randomly assigned a staple type (stainless steel or absorbable) immediately prior to closure of a TPLO skin incision. Incisions were compared for length, staple type and number, and an inflammation-infection score 2 weeks after surgery. RESULTS: Overall, 18.8% of incisions were diagnosed with inflammation or infection. No difference was found between inflammation-infection scores, incision length, number of staples used, or general anesthetic time between the 2 staple groups. However, wound closure was faster with stainless steel staples (22.50 seconds; range, 11-180) by approximately 30 seconds compared with absorbable staples (56.50 seconds; range, 18-190; P < .001). Time taken to close the incision correlated negatively with the number of occasions that absorbable staples were used (P = .01). CONCLUSION: Absorbable skin staples were successfully used to close skin incisions after TPLO and were not associated with an increased level of inflammation or infection in our clinical setting. CLINICAL SIGNIFICANCE: Absorbable staples may be considered to close surgical wounds when subsequent suture removal would be impractical, without specific concerns over inflammation or infection of the wound.


Subject(s)
Dog Diseases/epidemiology , Dogs/surgery , Infections/veterinary , Inflammation/veterinary , Osteotomy/veterinary , Surgical Stapling/veterinary , Sutures/veterinary , Tibia/surgery , Animals , Dog Diseases/prevention & control , Infection Control/methods , Infections/epidemiology , Inflammation/epidemiology , Inflammation/prevention & control , Random Allocation , Surgical Stapling/instrumentation , Wound Healing
6.
Sci Rep ; 8(1): 12257, 2018 08 16.
Article in English | MEDLINE | ID: mdl-30115938

ABSTRACT

This pilot study investigates a novel approach towards efficacy testing of antimicrobial cleaning agents; focusing primarily on hydrogen peroxide vapour (HPV). Contaminated surfaces are recognised modes of pathogen transmission within healthcare environments and increase the risk of pathogen acquisition in newly admitted patients. Studies have shown these pathogens can survive on surfaces for extended periods of time in spite of cleaning. This resilience is characteristic of biofilm formation and recent publications have identified their presence in hospitals. In this study, biofilm models comprised of multidrug-resistant organisms (MDROs) were generated using a drip flow reactor and exposed to HPV decontamination. The MDROs included Acinetobacter baumannii, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. Upon exposure, samples were periodically removed and enumerated to generate kill curves for each species. Consequently revealing any inherent resistances; such as catalase-producing organisms which expressed reduced susceptibility. Epifluorescence microscopy revealed an abundance of viable and non-viable microcolonies before and after decontamination, respectively. Greater than 6-Log10 reduction was achieved within a 100 minutes exposure time. This pilot study puts forward a potential methodology for testing antimicrobial agents against biofilms and supports the efficacy of HPV.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Biomimetics , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/pharmacology , Biofilms/growth & development , Drug Resistance, Multiple/drug effects , Volatilization
7.
Vet J ; 238: 1-9, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30103909

ABSTRACT

Psychiatric comorbidities affect a large percentage of people with epilepsy and have a detrimental impact on their quality of life. Recently, behavioural comorbidities, with similar characteristics to human psychiatric diseases, have been identified in dogs with idiopathic epilepsy. In particular, behaviours motivated by the fear-anxiety emotional system have been found to be associated with the occurrence of idiopathic epilepsy in both dogs receiving anti-epileptic drugs, and drug-naïve dogs. There has been little research into the relationship between epilepsy and behavioural signs, and even less into potential treatment protocols. The following article will review available literature from human medicine to describe the current state of knowledge about the bi-directional relationship between anxiety and epilepsy, draw parallels from reported anxiogenic and anxiolytic properties of anti-epileptic drugs and attempt to provide pharmaceutical and behavioural guidance for veterinary patients with epilepsy and comorbid anxiety.


Subject(s)
Anxiety , Dog Diseases/therapy , Dogs/psychology , Epilepsy/veterinary , Animals , Anti-Anxiety Agents/therapeutic use , Anticonvulsants/therapeutic use , Cognitive Behavioral Therapy , Comorbidity , Epilepsy/drug therapy , Quality of Life
8.
Dev Biol ; 426(2): 360-373, 2017 06 15.
Article in English | MEDLINE | ID: mdl-27471010

ABSTRACT

Unlike adult mammals, adult frogs regrow their optic nerve following a crush injury, making Xenopus laevis a compelling model for studying the molecular mechanisms that underlie neuronal regeneration. Using Translational Ribosome Affinity Purification (TRAP), a method to isolate ribosome-associated mRNAs from a target cell population, we have generated a transcriptional profile by RNA-Seq for retinal ganglion cells (RGC) during the period of recovery following an optic nerve injury. Based on bioinformatic analysis using the Xenopus laevis 9.1 genome assembly, our results reveal a profound shift in the composition of ribosome-associated mRNAs during the early stages of RGC regeneration. As factors involved in cell signaling are rapidly down-regulated, those involved in protein biosynthesis are up-regulated alongside key initiators of axon development. Using the new genome assembly, we were also able to analyze gene expression profiles of homeologous gene pairs arising from a whole-genome duplication in the Xenopus lineage. Here we see evidence of divergence in regulatory control among a significant proportion of pairs. Our data should provide a valuable resource for identifying genes involved in the regeneration process to target for future functional studies, in both naturally regenerative and non-regenerative vertebrates.


Subject(s)
Eye Proteins/biosynthesis , Gene Expression Regulation , Nerve Regeneration/physiology , Nerve Tissue Proteins/biosynthesis , Optic Nerve Injuries/physiopathology , Xenopus Proteins/biosynthesis , Xenopus laevis/genetics , Amino Acid Sequence , Animals , Animals, Genetically Modified , Eye Proteins/genetics , Gene Ontology , Molecular Sequence Annotation , Nerve Crush , Nerve Tissue Proteins/genetics , RNA, Messenger/genetics , RNA, Messenger/isolation & purification , Retinal Ganglion Cells/metabolism , Ribosomes/metabolism , Sequence Alignment , Sequence Analysis, RNA , Sequence Homology, Amino Acid , Signal Transduction , Xenopus Proteins/genetics , Xenopus laevis/physiology
9.
Lett Appl Microbiol ; 63(3): 178-82, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27324207

ABSTRACT

UNLABELLED: A comparative study was made on the efficacy of 5, 10 and 35% weight by weight (w/w) hydrogen peroxide solutions when applied using an automated room disinfection system. Six-log biological indicators of methicillin-resistant Staphylococcus aureus (MRSA) and Geobacillus stearothermophilus were produced on stainless steel coupons and placed within a large, sealed, environmentally controlled enclosure. Five percent hydrogen peroxide was distributed throughout the enclosure using a Bioquell hydrogen peroxide vapour generator (BQ-50) for 40 min and left to reside for a further 200 min. Biological indicators were removed at 10-min intervals throughout the first 120 min of the process. The experiment was repeated for 10 and 35% hydrogen peroxide solutions. Five percent and 10% hydrogen peroxide solutions failed to achieve any reduction of MRSA, but achieved full kill of G. stearothermophilus spores at 70 and 40 min respectively. Thirty-five percent hydrogen peroxide achieved a 6-log reduction of MRSA after 30 min and full kill of G. stearothermophilus at 20 min. The concentration of 5% hydrogen peroxide within the enclosure after the 200-min dwell was measured at 9·0 ppm. This level exceeds the 15-min Short Term Exposure Limit (STEL) for hydrogen peroxide of 2·0 ppm. Users of automated hydrogen peroxide disinfection systems should review system efficacy and room re-entry protocols in light of these results. SIGNIFICANCE AND IMPACT OF THE STUDY: This research allows hospital infection control teams to consider the impact and risks of using low concentrations of hydrogen peroxide for disinfection within their facilities, and to question automated room disinfection system providers on the efficacy claims they make. The evidence that low concentration hydrogen peroxide solutions do not rapidly, autonomously break down, is in contradiction to the claims made by some hydrogen peroxide equipment providers and raises serious health and safety concerns. Facilities using hydrogen peroxide systems that claim autonomous break down of hydrogen peroxide should introduce monitoring procedures to ensure rooms are safe for re-entry and patient occupation.


Subject(s)
Disinfectants/pharmacology , Disinfection/methods , Geobacillus stearothermophilus/drug effects , Hydrogen Peroxide/pharmacology , Infection Control/methods , Methicillin-Resistant Staphylococcus aureus/drug effects , Disinfectants/metabolism , Humans , Hydrogen Peroxide/metabolism
10.
Br Dent J ; 219(7): 343-6, 2015 Oct 09.
Article in English | MEDLINE | ID: mdl-26450251

ABSTRACT

AIM: To provide baseline data on dental issues affecting residents from the perspective of care home managers to inform oral health local needs assessments and commissioning decisions. METHODS: A pre-piloted postal questionnaire was sent to all identified managers of adult care homes (1,832) in the West Midlands between February and April 2011. Quantitative analysis was complemented by seeking the views of care home managers regarding training and experience of, and access to, dental services. RESULTS: The response rate to the study was 63.9% (1,170/1,832). There were 194 responding care homes who reported that residents had problems accessing dental services. Nearly double the proportion of nursing care homes and care homes with residents with elderly mental impairment (EMI) reported problems accessing dental services compared with care homes without nursing care and non-EMI care homes. Issues raised included patient safety concerns, reservations regarding expertise of dental staff, difficulties with transporting residents and waiting times for treatment. CONCLUSION: The survey provided a snapshot of dental issues as reported by care home managers, these results should help inform both the dental profession and those who commission services about issues affecting the oral health of patients living in care homes.


Subject(s)
Administrative Personnel , Dental Care/standards , Dental Health Surveys , Health Services Accessibility , Health Services Needs and Demand , Home Care Services , Oral Health , Adult , Humans , Surveys and Questionnaires
11.
Br Dent J ; 219(7): 349-53, 2015 Oct 09.
Article in English | MEDLINE | ID: mdl-26450252

ABSTRACT

AIM: To determine the oral health status of a sample of care home residents and provide data to inform local needs assessments and commissioning decisions. METHODS: A stratified sampling methodology was used to sample care homes; residents were then selected at random and invited to participate. The survey consisted of a short questionnaire and a clinical examination; it attempted to capture data relating to current oral health status, treatment need and suitability for treatment. RESULTS: Of 1761 residents sampled, 848 residents (mean age: 80 years) were competent to and consented to participate in the survey. Of those who consented to a clinical examination, 56% were dentate and 43.6% edentate. Among dentate residents, there was a caries prevalence of 55.8%. Just over half of examined residents (52.7%) were thought to be in need of dental treatment, and potentially suitable to receive treatment. CONCLUSION: These findings document the current state of oral health of a sample of care home residents in the West Midlands and provide valuable data to help inform strategic commissioning decisions. The particular oral health needs of this population group must be considered.


Subject(s)
Dental Care for Aged/standards , Dental Health Surveys , Health Services Accessibility , Home Care Services , Needs Assessment , Oral Health , Tooth Diseases/epidemiology , Adult , Aged , Aged, 80 and over , Dental Care for Aged/statistics & numerical data , Female , Humans , Male , Middle Aged , Prevalence , Surveys and Questionnaires , United Kingdom/epidemiology , Young Adult
12.
Ecol Appl ; 24(2): 346-62, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24689146

ABSTRACT

Throughout the world, fragmentation of landscapes by human activities has constrained the opportunity for large herbivores to migrate. Conflict between people and wildlife results when migrating animals transmit disease to livestock, damage property, and threaten human safety. Mitigating this conflict requires understanding the forces that shape migration patterns. Bison Bos bison migrating from Yellowstone National Park into the state of Montana during winter and spring concern ranchers on lands surrounding the park because bison can transmit brucellosis (Brucella abortus) to cattle. Migrations have been constrained, with bison being lethally removed or moved back into the park. We developed a state-space model to support decisions on bison management aimed at mitigating conflict with landowners outside the park. The model integrated recent GPS observations with 22 years (1990-2012) of aerial counts to forecast monthly distributions and identify factors driving migration. Wintering areas were located along decreasing elevation gradients, and bison accumulated in wintering areas prior to moving to areas progressively lower in elevation. Bison movements were affected by time since the onset of snowpack, snowpack magnitude, standing crop, and herd size. Migration pathways were increasingly used over time, suggesting that experience or learning influenced movements. To support adaptive management of Yellowstone bison, we forecast future movements to evaluate alternatives. Our approach of developing models capable of making explicit probabilistic forecasts of large herbivore movements and seasonal distributions is applicable to managing the migratory movements of large herbivores worldwide. These forecasts allow managers to develop and refine strategies in advance, and promote sound decision-making that reduces conflict as migratory animals come into contact with people.


Subject(s)
Animal Migration/physiology , Bison/physiology , Ecosystem , Animals , Bayes Theorem , Environmental Monitoring , Models, Biological , Montana , Seasons
13.
Dev Dyn ; 241(12): 1960-72, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23074098

ABSTRACT

BACKGROUND: Translating Ribosome Affinity Purification (TRAP), a method recently developed to generate cell type-specific translational profiles, relies on creating transgenic lines of animals in which a tagged ribosomal protein is placed under regulatory control of a cell type-specific promoter. An antibody is then used to affinity purify the tagged ribosomes so that cell type-specific mRNAs can be isolated from whole tissue lysates. RESULTS: Here, cell type-specific transgenic lines were generated to enable TRAP studies for retinal ganglion cells and rod photoreceptors in the Xenopus laevis retina. Using real time quantitative PCR for assessing expression levels of cell type-specific mRNAs, the TRAP method was shown to selectively isolate mRNAs expressed in the targeted cell and was efficient at purifying mRNAs expressed at both high and low levels. Statistical measures used to distinguish cell type-specific RNAs from low level background and non-specific RNAs showed TRAP to be highly effective in Xenopus. CONCLUSIONS: TRAP can be used to purify mRNAs expressed in rod photoreceptors and retinal ganglion cells in X. laevis. The generated transgenic lines will enable numerous studies into the development, disease, and injury of the X. laevis retina.


Subject(s)
Eye Proteins/biosynthesis , Gene Expression Regulation/physiology , Photoreceptor Cells, Vertebrate/metabolism , Protein Biosynthesis/physiology , Retinal Ganglion Cells/metabolism , Xenopus Proteins/biosynthesis , Animals , Gene Expression Profiling/methods , Photoreceptor Cells, Vertebrate/cytology , RNA, Messenger/biosynthesis , Real-Time Polymerase Chain Reaction/methods , Retinal Ganglion Cells/cytology , Xenopus laevis
14.
Br J Biomed Sci ; 65(2): 109-18, 2008.
Article in English | MEDLINE | ID: mdl-19055117

ABSTRACT

In contrast to the idea that bacteriology was introduced as a tool for the diagnosis and management of the individual patient, this review highlights the work of the municipal bacteriological laboratory in the United Kingdom to illustrate how bacteriological laboratories were introduced as means to control community epidemic disease. Using the examples of municipal laboratories in Brighton, Bristol and Aberdeen, it shows how public health considerations of community infectious diseases such as diphtheria and typhoid dominated the early development and workload of the municipal laboratory, rather than examination of patients with pathological states of uncertain aetiology. It argues that this public health focus of the Medical Officer of Health limited the range of diagnostic tests carried out in such laboratories for over two decades. The growing number of pathogenic microbes being discovered in the late 19th century appears to have had little impact on the tests being carried out in the municipal laboratory. Municipal bacteriological facilities in three towns, a central municipal laboratory (in Brighton), a central university pathological department (Aberdeen) or a combination of both (Bristol) all provided the same limited set of tests. This restricted set of bacteriological examinations is likely to have diminished the value and status of bacteriology in what should have been a period of increasing scope.


Subject(s)
Bacteriology/history , Public Health/history , History, 19th Century , History, 20th Century , Humans , United Kingdom
15.
Langmuir ; 23(5): 2680-7, 2007 Feb 27.
Article in English | MEDLINE | ID: mdl-17266342

ABSTRACT

New measurements of the dependence of the surface charge on the pH and electrolyte concentration for three living human white blood cell lines that are the principal targets of the HIV-1 virus are reported. Comparison of the electrophoretic fingerprint (EF) pattern, especially the line of zero mobility, with that of reference colloids establishes the separate individual identities and shows that all three exhibit a zwitterionic surface. With the EF results as a guide, preliminary biological infectivity measurements showed that small polyvalent cations modulate the negative charge on the T-cell surface in a way that strongly affects the infection kinetics. H9 cells were exposed to an infectious virus (X4), and the data showed that HIV interaction with target cells is enhanced by physiological fluids. The nondestructive methodology described is generally applicable to characterization of the surface charge and determination of the colloidal stability of any aqueous charged colloidal system without reference to any model of the double layer.


Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/pharmacology , Anti-Infective Agents/pharmacology , CD4-Positive T-Lymphocytes/metabolism , Electrophoresis/methods , HIV Infections/drug therapy , Cell Line, Tumor , Colloids/chemistry , Electrolytes , Humans , Hydrogen-Ion Concentration , Kinetics , Lanthanum/chemistry , Lymphoma, T-Cell/metabolism , Models, Chemical
16.
Aliment Pharmacol Ther ; 24(5): 821-9, 2006 Sep 01.
Article in English | MEDLINE | ID: mdl-16918886

ABSTRACT

BACKGROUND: Stomach pain and discomfort have been reported since antiquity. AIM: To follow the time trends since the 18th century of dyspepsia, gastric ulcer, duodenal ulcer, and benign oesophageal disease to test when dyspepsia started to become a major clinical problem. METHODS: The annual in- and out-patient records of the last three centuries from the Scottish Royal Infirmaries of Edinburgh, Aberdeen, Glasgow and Dundee were analysed. In addition, dispensary attendances, clinicians' casebooks, students' notebooks and medical texts have been scrutinized for historic statistics of upper gastrointestinal disease. RESULTS: Dyspepsia was first recorded in the 1750s and increased markedly subsequently. Such dyspepsia persisted after gastric and duodenal ulcers appeared in the late 19th century and then declined again in the late 20th century. Non-ulcer dyspepsia has remained the commonest diagnosis made after endoscopy for stomach pain in the beginning of the 21st century. CONCLUSION: The current commonest diagnosis of stomach pain, dyspepsia dates from the mid-18th century. Any explanations of its causation need to consider this timing.


Subject(s)
Gastrointestinal Diseases/history , Ambulatory Care/history , Duodenal Ulcer/epidemiology , Duodenal Ulcer/history , Dyspepsia/epidemiology , Dyspepsia/history , Esophageal Diseases/epidemiology , Esophageal Diseases/history , Female , Gastrointestinal Diseases/epidemiology , History, 18th Century , History, 19th Century , History, 20th Century , Hospitalization , Humans , Male , Scotland/epidemiology , Stomach Ulcer/epidemiology , Stomach Ulcer/history
17.
Women Health ; 37(2): 89-108, 2003.
Article in English | MEDLINE | ID: mdl-12733555

ABSTRACT

In this paper, we examine reasons for declining both prenatal screening, and diagnosis among a small group of pregnant women in Victoria, Australia. Semi-structured questionnaires were used to elicit women's account of their refusals of offers during pregnancy. Previous literature suggests that women decline prenatal screening and diagnosis because they are against abortion and the medicalisation of pregnancy, and have conoerns about the health and well-being of their fetuses. Women in this study had similar reasons but they also had other reasons for declining. Most clearly was that related to 'risk' brought about by the prospect of knowledge gained from undertaking prenatal screening and diagnostic tests, which would cause emotional distress and lead to further difficult decisions. The results have implications for the development and expansion of prenatal screening and diagnosis for pregnant women in Australia and elsewhere. We are not suggesting that prenatal screening and diagnosis is a problem for all women or even most women. However, health service providers must provide information about prenatal screening and diagnosis that is appropriate for all pregnant women, presenting all options, including that of not having any screening or diagnostic test. In doing so we will be facilitating the opportunity for women to make an informed choice and acknowledging the existence and importance of this small, but concerned group of women.


Subject(s)
Mass Screening/statistics & numerical data , Pregnant Women/psychology , Prenatal Diagnosis/statistics & numerical data , Treatment Refusal , Adult , Anxiety , Australia , Decision Making , Female , Health Services Research , Humans , Mass Screening/psychology , Pregnancy , Prenatal Diagnosis/psychology , Risk Assessment , Surveys and Questionnaires , Women's Health
18.
Nat Neurosci ; 4(10): 981-8, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11544482

ABSTRACT

Growth factors synthesized and released by target tissues promote survival and differentiation of innervating neurons. This retrograde signal begins when growth factors bind receptors at nerve terminals. Activated receptors are then endocytosed and transported through the axon to the cell body. Here we show that the mitogen-activated protein kinase (MAPK) signaling pathways used by neurotrophins during retrograde signaling differ from those used following direct stimulation of the cell soma. During retrograde signaling, endocytosed neurotrophin receptors (Trks) activate the extracellular signal-related protein kinase 5 (Erk5) pathway, leading to nuclear translocation of Erk5, phosphorylation of CREB, and enhanced neuronal survival. In contrast, Erk1/2, which mediates nuclear responses following direct cell body stimulation, does not transmit a retrograde signal. Thus, the Erk5 pathway has a unique function in retrograde signaling. Differential activation of distinct MAPK pathways may enable an individual growth factor to relay information that specifies the location and the nature of stimulation.


Subject(s)
Cell Survival/physiology , MAP Kinase Signaling System/physiology , Mitogen-Activated Protein Kinases/metabolism , Nerve Growth Factors/metabolism , Neurons, Afferent/physiology , Animals , Axons/physiology , Cell Fractionation , Cells, Cultured , Cyclic AMP Response Element-Binding Protein/metabolism , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , Ganglia, Spinal/cytology , Genes, Reporter/genetics , Microscopy, Fluorescence , Mitogen-Activated Protein Kinase 7 , Phosphorylation , Protein Transport/physiology , Rats , Receptors, Nerve Growth Factor/metabolism , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism
19.
J Biol Chem ; 276(10): 7661-71, 2001 Mar 09.
Article in English | MEDLINE | ID: mdl-11113118

ABSTRACT

Vesicular monoamine transporter 2 is important for the accumulation of monoamine neurotransmitters into synaptic vesicles and histamine transport into secretory vesicles of the enterochromaffin-like cell of the gastric corpus. In this study we have investigated the mechanisms regulating the transcriptional activation of the rat vesicular monoamine transporter 2 (VMAT2) promoter in gastric epithelial cells. Maintenance of basal levels of transcription was dependent on the presence of SP1, cAMP-response element (CRE), and overlapping AP2/SP1 consensus sequences within the region of promoter from -86 to +1 base pairs (bp). Gastrin stimulation increased transcriptional activity, and responsiveness was shown to be dependent on the CRE (-33 to -26 bp) and AP2/SP1 (-61 to -48 bp) consensus sites but independent of the SP1 site at -86 to -81 bp. Gastrin-induced transcription was dependent on the cooperative interaction of an uncharacterized nuclear factor of approximately 23.3 kDa that bound to the putative AP2/SP1 site, CRE-binding protein (CREB), and CREB-binding protein/p300. Gastrin stimulation resulted in the increased binding of phosphorylated CREB to the promoter, but it did not result in the increased binding of the AP2/SP1-binding protein. The gastrin responsiveness of the promoter was shown to be dependent on both the protein kinase C and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-signaling pathways, which may converge on the AP2/SP1-binding protein.


Subject(s)
Epithelial Cells/metabolism , Gastric Mucosa/metabolism , Gastrins/metabolism , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Membrane Transport Proteins , Neuropeptides , Promoter Regions, Genetic , Transcriptional Activation , Adenovirus E1A Proteins/metabolism , Animals , Base Sequence , Binding Sites , Blotting, Western , Cell Line , Cell Nucleus/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , DNA/metabolism , DNA-Binding Proteins/metabolism , Enzyme Inhibitors/pharmacology , Humans , Luciferases/metabolism , MAP Kinase Signaling System , Molecular Sequence Data , Plasmids/metabolism , Protein Binding , Protein Kinase C/metabolism , Rats , Transcription Factor AP-2 , Transcription Factors/metabolism , Transcription, Genetic , Transfection , Ultraviolet Rays , Vesicular Biogenic Amine Transport Proteins , Vesicular Monoamine Transport Proteins
20.
Int J Eat Disord ; 27(3): 335-40, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10694720

ABSTRACT

OBJECTIVE: To determine whether there are seasonal fluctuations in eating pathology in a nonclinical population. METHOD: The Eating Attitudes Test (EAT) was completed by 322 subjects during winter and again during summer. Summer and winter responses were compared to investigate differences in EAT total and subscale scores and for individual EAT items. Numbers of subjects fluctuating across the seasons by more than 2 SDs of the cohort's scores were identified. RESULTS: The cohort showed no significant seasonal change on EAT-40 totals, EAT-26 totals, or within the EAT subscales. There were significant (p <.025) seasonal fluctuations on four of the EAT-40 questions. For individual respondents, there was no greater likelihood of scoring significantly higher in the winter than in the summer. DISCUSSION: Clinically significant seasonal fluctuations in eating pathology on the EAT did not occur in this nonclinical population. It is debatable whether items within the EAT which show significant seasonal fluctuations should be retained or discarded.


Subject(s)
Attitude , Feeding and Eating Disorders/diagnosis , Seasons , Adult , Cohort Studies , Feeding and Eating Disorders/psychology , Female , Humans , Male , Middle Aged , Reproducibility of Results , Surveys and Questionnaires
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