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1.
Eur J Dermatol ; 33(3): 218-229, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37594326

ABSTRACT

BACKGROUND: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) remain the most prevalent malignancies, contributing a higher workload to cancer registries than all cancers combined. The nature of skin cancers in addition to current coding methods employed by registries give a skewed representation of the workload. OBJECTIVES: A comprehensive search examining the incidence of BCC and/or cSCC at a regional or national level in the UK and Ireland was devised. Standardisation methods were grouped to permit comparison, and a bias assessment tool was employed. MATERIALS & METHODS: Sixteen UK and Republic of Ireland epidemiological studies on BCC/cSCC over a 48-year period were compiled, examining incidence, trends and emerging risk factors. RESULTS: Incidence of BCC within the UK is increasing annually by up to 4%, with rates in Wales increasing by up to 6.6% and 1.6% annually for BCC and cSCC, respectively. Inverse relationships are noted between BCC/cSCC and social deprivation. Although the elderly remain the most at risk, the 30-49 age group have illustrated growth rates of approximately 4%. CONCLUSION: This review outlines increasing incidence in the UK with higher rates noted in Wales, the Southeast, West and Central regions. Incidence rates are higher amongst the least socially deprived and an increasing incidence amongst younger age groups was found, however further trend analysis is required. A more comprehensive data collection method within registries is necessary to ensure accurate representation and fluid comparison. Service planning and public awareness campaigns must be implemented to prevent overwhelming future services.


Subject(s)
Carcinoma, Basal Cell , Carcinoma, Squamous Cell , Skin Neoplasms , Aged , Humans , Incidence , Skin Neoplasms/epidemiology , Carcinoma, Squamous Cell/epidemiology , Ireland/epidemiology , Carcinoma, Basal Cell/epidemiology , Wales
2.
J Racial Ethn Health Disparities ; 9(2): 620-629, 2022 04.
Article in English | MEDLINE | ID: mdl-33721290

ABSTRACT

Latinx in the USA experience disparities in morbidity and mortality when compared to their non-Hispanic White counterparts. Patient-centered culturally sensitive health care (PC-CSHC) has been deemed a best practice approach to alleviate and eliminate these disparities. However, literature on how Latinx patients perceive their care and what indicators of PC-CSHC may be most related to treatment outcomes is limited. This study collected data from 81 adult Latinx participants who had been admitted to an inpatient care unit to understand the following: (a) their perception of their providers' PC-CSHC in three different areas: Competence/Confidence, Sensitivity/Interpersonal, and Respect/Communication; (b) whether there are differences between English- and Spanish-speaking Latinx patients in their perception of their providers' PC-CSHC; and (c) whether these PC-CSHC indicators were associated to patient satisfaction, patient-provider communication, and therapeutic alliance. Participants were mostly male, older than 55 years of age, and working or lower class, with English as their primary language. Results showed that patients rated their providers' Competence (M = 3.57, SD = .46) higher than both Sensitivity, t(68) = .04, p = .04, (M = 3.49, SD =.54), and Respect, t(53) = 2.765, p = .008, (M = 3.38, SD = .57). English-speaking Latinx were overall less satisfied with their providers than Spanish-speaking Latinx, in particular in their communication. Finally, higher provider cultural sensitivity appears to be a predictor of patient satisfaction, patient-provider communication, and working alliance. Implications for refining provider trainings to treat this vulnerable and understudied (i.e., Latinx) population are discussed.


Subject(s)
Culturally Competent Care , Hispanic or Latino , Patient Satisfaction , Therapeutic Alliance , Adult , Communication , Female , Humans , Male , Middle Aged , Physician-Patient Relations
3.
Radiography (Lond) ; 26(3): e140-e145, 2020 08.
Article in English | MEDLINE | ID: mdl-32052754

ABSTRACT

INTRODUCTION: There is an increasing demand on diagnostic imaging departments, a shortage of radiologists, and a backlog of images requiring a report across several trusts in the UK. A negative impact on performance can result in significant outcomes for the patient. The aim of this study is to ascertain whether decisions made under time pressure will affect the accuracy of the interpretation of conventional radiographs. METHODS: Final year undergraduate diagnostic radiography students were recruited [n = 21] and separated into three groups of seven at random, assigning time limits per image for a set of normal and abnormal conventional appendicular radiographs; 15 s (high pressure), 30 s (moderate pressure) and unlimited time (low pressure). Each image was assessed, and answers were recorded as normal or abnormal with an approximate location of the pathology. RESULTS: The ANOVA test revealed no statistical significance amongst results. The mean accuracy was highest in the 15 s group (82.86%) and lowest in the unlimited time group (74.52%). The results also demonstrated a decrease in accuracy with increased image review times within the unlimited time group; with the quickest participant achieving 88.33% and the slowest, 56.67%. CONCLUSION: The results demonstrated no statistical significance. However, it is recommended to conduct a similar study using sufficient reporting practitioners to enable direct parallels to be drawn with statistical significance. IMPLICATIONS FOR PRACTICE: The results signify an importance for imaging departments to manage the number of staff and their workload. Subsequently, this aims to ensure reporting practitioners work at their optimum stress level for efficient work performance.


Subject(s)
Clinical Competence/statistics & numerical data , Image Interpretation, Computer-Assisted/methods , Radiology/education , Students, Medical/statistics & numerical data , Wounds and Injuries/diagnostic imaging , Female , Humans , Male , Pilot Projects , Reproducibility of Results , Sensitivity and Specificity , Time , United Kingdom
4.
Br J Dermatol ; 182(5): 1136-1147, 2020 05.
Article in English | MEDLINE | ID: mdl-31529485

ABSTRACT

BACKGROUND: Previous studies have identified an inverse association between melanoma and smoking; however, data from population-based studies are scarce. OBJECTIVES: To determine the association between smoking and socioeconomic (SES) on the risk of development of melanoma. Furthermore, we sought to determine the implications of smoking and SES on survival. METHODS: We conducted a population-based case-control study. Cases were identified from the Welsh Cancer Intelligence and Surveillance Unit (WCISU) during 2000-2015 and controls from the general population. Smoking and SES were obtained from data linkage with other national databases. The association of smoking status and SES on the incidence of melanoma were assessed using binary logistic regression. Multivariate survival analysis was performed on a melanoma cohort using a Cox proportional hazard model using survival as the outcome. RESULTS: During 2000-2015, 9636 patients developed melanoma. Smoking data were obtained for 7124 (73·9%) of these patients. There were 26 408 controls identified from the general population. Smoking was inversely associated with melanoma incidence [odds ratio (OR) 0·70, 95% confidence interval (CI) 0·65-0·76]. Smoking was associated with an increased overall mortality [hazard ratio (HR) 1·30, 95% CI 1·09-1·55], but not associated with melanoma-specific mortality. Patients with higher SES had an increased association with melanoma incidence (OR 1·58, 95% CI 1·44-1·73). Higher SES was associated with an increased chance of both overall (HR 0·67, 95% CI 0·56-0·81) and disease-specific survival (HR 0·69, 95% CI 0·53-0·90). CONCLUSIONS: Our study has demonstrated that smoking appeared to be associated with reduced incidence of melanoma. Although smoking increases overall mortality, no association was observed with melanoma-specific mortality. Further work is required to determine if there is a biological mechanism underlying this relationship or an alternative explanation, such as survival bias. What's already known about this topic? Previous studies have been contradictory with both negative and positive associations between smoking and the incidence of melanoma reported. Previous studies have either been limited by publication bias because of selective reporting or underpowered. What does this study add? Our large study identified an inverse association between smoking status and melanoma incidence. Although smoking status was negatively associated with overall disease survival, no significant association was noted in melanoma-specific survival. Socioeconomic status remains closely associated with melanoma. Although higher socioeconomic populations are more likely to develop the disease, patients with lower socioeconomic status continue to have a worse prognosis.


Subject(s)
Melanoma , Skin Neoplasms , Case-Control Studies , Humans , Incidence , Information Storage and Retrieval , Melanoma/epidemiology , Melanoma/etiology , Skin Neoplasms/epidemiology , Skin Neoplasms/etiology , Smoking/adverse effects , Social Class
5.
Br J Oral Maxillofac Surg ; 57(9): 847-856, 2019 11.
Article in English | MEDLINE | ID: mdl-31615708

ABSTRACT

This is the third of three articles that give an overview of the current evidence for management of the neck and parotid in patients with cutaneous cancers of the head and neck. In this paper we discuss Merkel cell carcinoma (MCC) and review the latest evidence for management of the regional nodes.


Subject(s)
Carcinoma, Merkel Cell , Skin Neoplasms , Carcinoma, Merkel Cell/therapy , Head and Neck Neoplasms/therapy , Humans , Lymph Nodes , Lymphatic Metastasis , Neoplasm Staging , Sentinel Lymph Node Biopsy , Skin Neoplasms/therapy
6.
Clin Oncol (R Coll Radiol) ; 31(2): 81-90, 2019 02.
Article in English | MEDLINE | ID: mdl-30385006

ABSTRACT

The burden of human papillomavirus (HPV)-related cancers worldwide is significant. Although the incidence of cervical cancer is decreasing due to cervical screening programmes, the incidences of oropharyngeal, anal and vulval cancers are increasing. The introduction of HPV vaccination programmes in many countries has had an impact on HPV infection rates but due to the time-lag from initial HPV infection to the development of invasive carcinoma, the impact on the incidence of HPV-related cancer will take more time to become evident. This review explores the common aspects of HPV-related cancers and how they differ from their HPV-negative counterparts, both clinically and molecularly. It also covers the implications this has on future treatment strategies, including the possible role of immunotherapy.


Subject(s)
Anus Neoplasms/virology , Early Detection of Cancer/methods , Oropharyngeal Neoplasms/virology , Papillomaviridae/pathogenicity , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virology , Female , Humans , Male
7.
Int J Cosmet Sci ; 39(5): 543-549, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28594472

ABSTRACT

OBJECTIVE: The objective of this work was to create a shampoo formula that contains a stable ordered gel network structure that delivers fatty alcohols inside hair. METHODS: X-ray diffraction (SAXS and WAXS), SEM and DSC have been used to confirm formation of the ordered Lß gel network with fatty alcohol (cetyl and stearyl alcohols) and an anionic surfactant (SLE1S). Micro-autoradiography and extraction methods using GC-MS were used to confirm penetration of fatty alcohols into hair, and cyclic fatigue testing was used to measure hair strength. RESULTS: In this work, evidence of a stable Lß ordered gel network structure created from cetyl and stearyl alcohols and anionic surfactant (SLE1S) is presented, and this is confirmed via scanning electron microscopy images showing lamella layers and differential scanning calorimetry (DSC) showing new melting peaks vs the starting fatty alcohols. Hair washed for 16 repeat cycles with this shampoo showed penetration of fatty alcohols from the gel network into hair as confirmed by a differential extraction method with GC-MS and by radiolabelling of stearyl alcohol and showing its presence inside hair cross-sections. The gel network role in delivering fatty alcohol inside hair is demonstrated by comparing with a shampoo with added fatty alcohol not in an ordered gel network structure. The hair containing fatty alcohol was measured via the Dia-stron cyclic fatigue instrument and showed a significantly higher number of cycles to break vs control. CONCLUSIONS: The formation of a stable gel network was confirmed in the formulated shampoo, and it was demonstrated that this gel network is important to deliver cetyl and stearyl alcohols into hair. The presence of fatty alcohol inside hair was shown to deliver a hair strength benefit via cyclic fatigue testing.


Subject(s)
Gels , Hair Preparations , Hair , Calorimetry, Differential Scanning , Fatty Alcohols/analysis , Gas Chromatography-Mass Spectrometry , Humans , Microscopy, Electron, Scanning , Surface-Active Agents/analysis , X-Ray Diffraction
8.
J Laryngol Otol ; 130(S2): S125-S132, 2016 May.
Article in English | MEDLINE | ID: mdl-27841126

ABSTRACT

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides consensus recommendations on the management of cutaneous basal cell carcinoma and squamous cell carcinoma in the head and neck region on the basis of current evidence. Recommendations • Royal College of Pathologists minimum datasets for NMSC should be adhered to in order to improve patient care and help work-force planning in pathology departments. (G) • Tumour depth is of critical importance in identifying high-risk cutaneous squamous cell carcinoma (cSCC), and should be reported in all cases. (R) • Appropriate imaging to determine the extent of primary NMSC is indicated when peri-neural involvement or bony invasion is suspected. (R) • In the clinically N0 neck, radiological imaging is not beneficial, and a policy of watchful waiting and patient education can be adopted. (R) • Patients with high-risk NMSC should be treated by members of a skin cancer multidisciplinary team (MDT) in secondary care. (G) • Non-infiltrative basal cell carcinoma (BCC) <2 cm in size should be excised with a margin of 4-5 mm. Smaller margins (2-3 mm) may be taken in sites where reconstructive options are limited, when reconstruction should be delayed. (R) • Where there is a high risk of recurrence, delayed reconstruction or Mohs micrographic surgery should be used. (R) • Surgical excision of low-risk cSCC with a margin of 4 mm or greater is the treatment of choice. (R) • High-risk cSCC should be excised with a margin of 6 mm or greater. (R). • Mohs micrographic surgery has a role in some high-risk cSCC cases following MDT discussion. (R) • Delayed reconstruction should be used in high-risk cSCC. (G) • Intra-operative conventional frozen section in cSCC is not recommended. (G) • Radiotherapy (RT) is an effective therapy for primary BCC and cSCC. (R) • Re-excision should be carried out for incompletely excised high-risk BCC or where there is deep margin involvement. (R) • Incompletely excised high-risk cSCC should be re-excised. (R) • Further surgery should involve confirmed marginal clearance before reconstruction. (R) • P+ N0 disease: Resection should include involved parotid tissue, combined with levels I-III neck dissection, to include the external jugular node. (R) • P+ N+ disease: Resection should include level V if that level is clinically or radiologically involved. (R) • Adjuvant RT should include level V if not dissected. (R) • P0 N+ disease: Anterior neck disease should be managed with levels I-IV neck dissection to include the external jugular node. (R) • P0 N+ posterior echelon nodal disease (i.e. occipital or post-auricular) should undergo dissection of levels II-V, with sparing of level I. (R) • Consider treatment of the ipsilateral parotid if the primary site is the anterior scalp, temple or forehead. (R) • All patients should receive education in self-examination and skin cancer prevention measures. (G) • Patients who have had a single completely excised BCC or low-risk cSCC can be discharged after a single post-operative visit. (G) • Patients with an excised high-risk cSCC should be reviewed three to six monthly for two years, with further annual review depending upon clinical risk. (G) • Those with recurrent or multiple BCCs should be offered annual review. (G).


Subject(s)
Carcinoma, Basal Cell/diagnosis , Carcinoma, Squamous Cell/diagnosis , Head and Neck Neoplasms/diagnosis , Skin Neoplasms/diagnosis , Carcinoma, Basal Cell/pathology , Carcinoma, Basal Cell/surgery , Carcinoma, Basal Cell/therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/therapy , Combined Modality Therapy/standards , Dermatologic Surgical Procedures/standards , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Head and Neck Neoplasms/therapy , Humans , Interdisciplinary Communication , Lymphatic Metastasis/diagnosis , Lymphatic Metastasis/pathology , Neoplasm Staging/standards , Patient Care Team/standards , Skin/pathology , Skin Neoplasms/pathology , Skin Neoplasms/surgery , Skin Neoplasms/therapy , United Kingdom
9.
Sci Rep ; 6: 35211, 2016 11 04.
Article in English | MEDLINE | ID: mdl-27811959

ABSTRACT

In this study the laws of mechanics for multi-component systems are used to develop a theory for the diffusion of ions in the presence of an electrostatic field. The analysis begins with the governing equation for the species velocity and it leads to the governing equation for the species diffusion velocity. Simplification of this latter result provides a momentum equation containing three dominant forces: (a) the gradient of the partial pressure, (b) the electrostatic force, and (c) the diffusive drag force that is a central feature of the Maxwell-Stefan equations. For ideal gas mixtures we derive the classic Nernst-Planck equation. For liquid-phase diffusion we encounter a situation in which the Nernst-Planck contribution to diffusion differs by several orders of magnitude from that obtained for ideal gases.

10.
Clin Exp Dermatol ; 41(2): 156-8, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26132338

ABSTRACT

Multifocal capillary malformation (CM) is the cardinal feature of patients with RASA1 mutations. These CMs are 'red flags', signalling the possible association with an arteriovenous malformation (AVM) or an arteriovenous fistula (AVF). We report an 8-year-old boy who presented with > 20 CMs, who was found to have a novel mutation in the RASA1 gene. Radiological screening of children with RASA1 mutations is not standardized, and we elected to carry out baseline magnetic resonance imaging of the brain and spine in our case, which gave normal results. We discuss the recent literature and our approach in the management of such a case.


Subject(s)
Capillaries/abnormalities , Mutation , Vascular Malformations/genetics , p120 GTPase Activating Protein/genetics , Child , Exons , Humans , Male
12.
Ann R Coll Surg Engl ; 94(4): e174-6, 2012 May.
Article in English | MEDLINE | ID: mdl-22613293

ABSTRACT

The incidence of malignant melanoma is increasing and the management of metastatic disease remains a challenge to clinicians. We describe three cases where surgical management of metastases has resulted in prolonged survival.


Subject(s)
Melanoma/surgery , Skin Neoplasms , Adult , Fatal Outcome , Humans , Lymphatic Metastasis , Male , Melanoma/secondary , Middle Aged , Neoplasm Metastasis
13.
Br J Radiol ; 84(1007): 967-96, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22011829

ABSTRACT

Volumetric modulated arc therapy (VMAT) is a novel radiation technique, which can achieve highly conformal dose distributions with improved target volume coverage and sparing of normal tissues compared with conventional radiotherapy techniques. VMAT also has the potential to offer additional advantages, such as reduced treatment delivery time compared with conventional static field intensity modulated radiotherapy (IMRT). The clinical worldwide use of VMAT is increasing significantly. Currently the majority of published data on VMAT are limited to planning and feasibility studies, although there is emerging clinical outcome data in several tumour sites. This article aims to discuss the current use of VMAT techniques in practice and review the available data from planning and clinical outcome studies in various tumour sites including prostate, pelvis (lower gastrointestinal, gynaecological), head and neck, thoracic, central nervous system, breast and other tumour sites.


Subject(s)
Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted/instrumentation , Radiotherapy, Intensity-Modulated/instrumentation , Breast Neoplasms/radiotherapy , Central Nervous System Neoplasms/radiotherapy , Digestive System Neoplasms/radiotherapy , Female , Genital Neoplasms, Female/radiotherapy , Head and Neck Neoplasms/radiotherapy , Humans , Male , Prostatic Neoplasms/radiotherapy , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Thoracic Neoplasms/radiotherapy
15.
Neural Dev ; 6: 20, 2011 May 03.
Article in English | MEDLINE | ID: mdl-21539742

ABSTRACT

BACKGROUND: The concept of an equivalence group, a cluster of cells with equal potential to adopt the same specific fate, has served as a useful paradigm to understand neural cell type specification. In the Drosophila eye, a set of five cells, called the 'R7 equivalence group', generates a single photoreceptor neuron and four lens-secreting epithelial cells. This choice between neuronal versus non-neuronal cell fates rests on differential requirements for, and cross-talk between, Notch/Delta- and Ras/mitogen-activated protein kinase (MAPK)-dependent signaling pathways. However, many questions remain unanswered related to how downstream events of these two signaling pathways mediate distinct cell fate decisions. RESULTS: Here, we demonstrate that two direct downstream targets of Ras and Notch signaling, the transcription factors Prospero and dPax2, are essential regulators of neuronal versus non-neuronal cell fate decisions in the R7 equivalence group. Prospero controls high activated MAPK levels required for neuronal fate, whereas dPax2 represses Delta expression to prevent neuronal fate. Importantly, activity from both factors is required for proper cell fate decisions to occur. CONCLUSIONS: These data demonstrate that Ras and Notch signaling are integrated during cell fate decisions within the R7 equivalence group through the combinatorial and opposing activities of Pros and dPax2. Our study provides one of the first examples of how the differential expression and synergistic roles of two independent transcription factors determine cell fate within an equivalence group. Since the integration of Ras and Notch signaling is associated with many developmental and cancer models, these findings should provide new insights into how cell specificity is achieved by ubiquitously used signaling pathways in diverse biological contexts.


Subject(s)
Drosophila Proteins/metabolism , Drosophila Proteins/physiology , Nerve Tissue Proteins/physiology , Neurons/physiology , Nuclear Proteins/physiology , PAX2 Transcription Factor/physiology , Receptors, Notch/metabolism , Signal Transduction/physiology , Transcription Factors/physiology , ras Proteins/metabolism , Animals , Animals, Genetically Modified , Cell Differentiation/genetics , Drosophila , Drosophila Proteins/genetics , Eye/cytology , Eye/embryology , Eye/metabolism , Gene Expression Regulation, Developmental/genetics , Nerve Tissue Proteins/genetics , Neurons/classification , Nuclear Proteins/genetics , PAX2 Transcription Factor/genetics , Photoreceptor Cells , Pupa , Receptors, Notch/genetics , Retina/cytology , Retinal Cone Photoreceptor Cells/cytology , Retinal Cone Photoreceptor Cells/physiology , Transcription Factors/genetics , ras Proteins/genetics
16.
Occup Med (Lond) ; 61(3): 152-6, 2011 May.
Article in English | MEDLINE | ID: mdl-21427030

ABSTRACT

AIMS: To assess any recent change in the quantity of teaching of occupational medicine (OM) in UK undergraduate medical curricula, and to compare these results with those obtained in previous years. METHODS: A questionnaire survey designed to capture information on the teaching of OM to undergraduates in all medical schools listed in the UK Universities and Colleges Admissions Service prospectus for 2008-09. RESULTS: Twenty-one of 32 (66%) UK medical schools returned a completed questionnaire. A comparison of results from this survey, with previous surveys, of teaching of OM to undergraduates in the UK showed that fewer schools now provide lectures, project work or ward-based tuition in this subject, than previously. In contrast to previous surveys, workplace visits were not undertaken by any institution. Only three (15%) of the schools setting an examination question related to OM also had a syllabus or explicit learning outcomes. More schools reported incorporating OM teaching within the teaching of other subjects. CONCLUSIONS: Despite the increasing recognition of the impact and value of work on health and the growing evidence base to support work as a means of enhancing health, medical schools fall far short of a comprehensive programme of teaching in this important subject area. This may result in doctors being poorly prepared to recognize and diagnose occupational diseases adequately, and poorly equipped to support their patients in, for example, return to work, rehabilitation or providing advice on fitness to work.


Subject(s)
Education, Medical, Undergraduate/statistics & numerical data , Occupational Medicine/education , Schools, Medical/statistics & numerical data , Curriculum/standards , Education, Medical, Undergraduate/methods , Humans , Occupational Medicine/statistics & numerical data , Surveys and Questionnaires , United Kingdom
17.
Neuroscience ; 171(4): 1041-53, 2010 Dec 29.
Article in English | MEDLINE | ID: mdl-20888396

ABSTRACT

The presynaptic, hemicholinium-3 sensitive, high-affinity choline transporter (CHT) supplies choline for acetylcholine (ACh) synthesis. In mice, a homozygous deletion of CHT (CHT-/-) leads to premature cessation of spontaneous or evoked neuromuscular signaling and is associated with perinatal cyanosis and lethality within 1 h. Heterozygous (CHT+/-) mice exhibit diminished brain ACh levels and demonstrate an inability to sustain vigorous motor activity. We sought to explore the contribution of CHT gene dosage to motor function in greater detail using transgenic mice where CHT is expressed under control of the motor neuron promoter Hb9 (Hb9:CHT). On a CHT-/- background, the Hb9:CHT transgene conferred mice with the ability to move and breath for a postnatal period of ∼24 h, thus increasing survival. Conversely, Hb9:CHT expression on a wild-type background (CHT+/+;Hb9:CHT) leads to an increased capacity for treadmill running compared to wild-type littermates. Analysis of the stimulated compound muscle action potential (CMAP) in these animals under basal conditions established that CHT+/+;Hb9:CHT mice display an unexpected, bidirectional change, producing either elevated or reduced CMAP amplitude, relative to CHT+/+ animals. To examine whether these two groups arise from underlying changes in synaptic properties, we used high-frequency stimulation of motor axons to assess CMAP recovery kinetics. Although CHT+/+; Hb9:CHT mice in the two groups display an equivalent, time-dependent reduction in CMAP amplitude, animals with a higher basal CMAP amplitude demonstrate a significantly enhanced rate of recovery. To explain our findings, we propose a model whereby CHT support for neuromuscular signaling involves contributions to ACh synthesis as well as cholinergic synaptic vesicle availability.


Subject(s)
Membrane Transport Proteins/metabolism , Motor Activity/physiology , Motor Neurons/cytology , Motor Neurons/metabolism , Synapses/metabolism , Acetylcholine/pharmacology , Acetylcholinesterase/metabolism , Action Potentials/genetics , Animals , Animals, Newborn , Behavior, Animal , Brain/cytology , Choline O-Acetyltransferase/metabolism , Electric Stimulation/methods , Exercise Test/methods , GPI-Linked Proteins/metabolism , Gene Expression Regulation, Developmental/genetics , Green Fluorescent Proteins/genetics , Homeodomain Proteins/genetics , Membrane Transport Proteins/genetics , Mice , Mice, Transgenic , Motor Activity/genetics , Muscle, Skeletal/physiology , Nerve Tissue Proteins , Neuromuscular Junction/metabolism , Statistics, Nonparametric , Transcription Factors/genetics
19.
Behav Processes ; 77(1): 33-42, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17628349

ABSTRACT

Rats were trained on mixed-fixed-interval (FI) schedules, with component FIs of 30 and 60s. The probability of reinforcement according to FI 30s varied between conditions, across values of 0.1, 0.3, 0.5, 0.7 and 0.9. When response rate in the 60s intervals was measured, separate response peaks, one close to 30s, the other at 60s, could be identified when the probability of reinforcement at 30s was 0.3 or greater. Nonlinear regression found that the location of the earlier peak was always close to 30s, that the coefficient of variation of the response functions at 30 and 60s were unaffected by reinforcement probability, but that the 30s component appeared to be timed slightly more precisely than the 60s one. Response rate at around 30s increased with increasing probability of reinforcement according to FI 30s, but responding at 60s was unaffected by reinforcement probability. The data are discussed with respect to a number of contemporary models of animal timing (scalar expectancy theory, the Behavioural Theory of Timing and the Learning to Time model), and a recent account of response output on FI-like schedules.


Subject(s)
Reinforcement, Psychology , Time Perception , Animals , Behavior, Animal , Male , Rats , Reinforcement Schedule
20.
FEBS Lett ; 580(5): 1479-84, 2006 Feb 20.
Article in English | MEDLINE | ID: mdl-16466721

ABSTRACT

The long-wavelength sensitive (red) opsin genes encode proteins which play a central role in daytime and color vision in vertebrates. We used transgenic Xenopus to identify 5' cis-elements in the red cone opsin promoter necessary for cone-specific expression. We found a highly conserved extended region (-725 to -173) that was required for restricting GFP transgene expression to cones. We further identified a short element (5'-CCAATTAAGAGAT-3') highly conserved amongst tetrapods, including humans, necessary to restrict expression to cones in the retina. These results identify novel conserved elements that regulate spatial expression of tetrapod red cone opsin genes.


Subject(s)
Enhancer Elements, Genetic , Gene Expression Regulation , Promoter Regions, Genetic , Retinal Cone Photoreceptor Cells , Rod Opsins/genetics , 5' Flanking Region , Amino Acid Sequence , Animals , Animals, Genetically Modified , Conserved Sequence , Xenopus laevis
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