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1.
Am J Physiol Gastrointest Liver Physiol ; 320(6): G1093-G1104, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33908261

RESUMO

Constipation and abdominal pain are commonly encountered in opioid-induced bowel dysfunction (OBD). The underlying mechanisms are incompletely understood, and treatments are not satisfactory. As patients with OBD often have fecal retention, we aimed to determine whether fecal retention plays a pathogenic role in the development of constipation and abdominal pain in OBD, and if so to investigate the mechanisms. A rodent model of OBD was established by daily morphine treatment at 10 mg/kg for 7 days. Bowel movements, colonic muscle contractility, visceromotor response to colorectal distention, and cell excitability of colon-projecting dorsal root ganglion neurons were determined in rats fed with normal pellet food, or with clear liquid diet. Morphine treatment (Mor) reduced fecal outputs starting on day 1, and caused fecal retention afterward. Compared with controls, Mor rats demonstrated suppressed muscle contractility, increased neuronal excitability, and visceral hypersensitivity. Expression of cyclooxygenase-2 (COX-2) and nerve growth factor (NGF) was upregulated in the smooth muscle of the distended colon in Mor rats. However, prevention of fecal retention by feeding rats with clear liquid diet blocked upregulation of COX-2 and NGF, restored muscle contractility, and attenuated visceral hypersensitivity in Mor rats. Moreover, inhibition of COX-2 improved smooth muscle function and fecal outputs, whereas anti-NGF antibody administration attenuated visceral hypersensitivity in Mor rats. Morphine-induced fecal retention is an independent pathogenic factor for motility dysfunction and visceral hypersensitivity in rats with OBD. Liquid diet may have therapeutic potential for OBD by preventing fecal retention-induced mechanotranscription of COX-2 and NGF.NEW & NOTEWORTHY Our preclinical study shows that fecal retention is a pathogenic factor in opioid-induced bowel dysfunction, as prevention of fecal retention with liquid diet improved motility and attenuated visceral hyperalgesia in morphine-treated animals by blocking expression of cyclooxygenase-2 and nerve growth factor in the colon.


Assuntos
Motilidade Gastrointestinal/fisiologia , Hiperalgesia/fisiopatologia , Morfina/farmacologia , Constipação Induzida por Opioides/fisiopatologia , Animais , Ciclo-Oxigenase 2/metabolismo , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Hiperalgesia/metabolismo , Masculino , Fator de Crescimento Neural/metabolismo , Constipação Induzida por Opioides/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Opioides/metabolismo , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/metabolismo
2.
Death Stud ; 45(9): 746-750, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-31596178

RESUMO

To further inclusion of interpersonal hopelessness within the interpersonal theory of suicide, we evaluated the Interpersonal Hopelessness Scale's (IHS) factor structure, and compared its relation to suicide ideation to that of the Interpersonal Needs Questionnaire's. Participants were 591 attentive US adults who completed surveys online. Exploratory factor analyses supported a single IHS factor, which accounted for about 70% of the total variance. Both measures statistically predicted suicide ideation; the IHS explained slightly more variation in suicide ideation scores. Including interpersonal hopelessness within measures of the interpersonal theory's constructs may prove important in developing suicide risk assessment and treatment.


Assuntos
Relações Interpessoais , Ideação Suicida , Adulto , Afeto , Humanos , Teoria Psicológica , Fatores de Risco , Autoimagem
3.
Pain Med ; 19(9): 1782-1789, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29016893

RESUMO

Objectives: The goal of this study was to assess the success of the morphine microdose method in a community pain clinic setting by monitoring follow-up frequency, dose escalation, and monotherapy/polytherapy ratio. The morphine microdose method involves a pretrial reduction or elimination of systemic opioids followed by a period of abstinence. Intrathecal (IT) morphine is then started at doses of less than 0.2 mg per day. Systemic opioid abstinence is then continued after pump implant and IT morphine monotherapy. Design: Retrospective review of medical records. Setting: Private and academic pain clinic practices. Subjects: Chronic noncancer pain patients. Methods: We reviewed the charts of 60 patients who had completed a microdose regimen and had an IT pump implanted between June 11, 2008, and October 11, 2014. During IT therapy, dose change over time, pain scores, side effects, max dose, and duration were recorded. Results: The majority of patients (35/60, 58%) were successfully managed solely on morphine microdose monotherapy. These patients did not require additional oral therapy. There was a significant reduction in mean pain scores, from 7.4 ± 0.32 before microdose therapy to 4.8 ± 0.3 after microdose therapy. Conclusions: Microdose therapy achieved analgesia, improved safety, and avoided systemic side effects. The safety of IT therapy was increased by using a lower concentration (2 mg/mL) and lower daily doses (<3 mg/d) of morphine. Furthermore, microdose therapy was feasible, safe, and cost-effective in the outpatient setting.


Assuntos
Analgésicos Opioides/administração & dosagem , Dor Crônica/tratamento farmacológico , Morfina/administração & dosagem , Manejo da Dor/métodos , Idoso , Feminino , Humanos , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
Biophys J ; 112(2): 300-312, 2017 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-28122216

RESUMO

Slow deactivation of hERG channels is critical for preventing cardiac arrhythmia yet the mechanistic basis for the slow gating transition is unclear. Here, we characterized the temporal sequence of events leading to voltage sensor stabilization upon membrane depolarization. Progressive increase in step depolarization duration slowed voltage-sensor return in a biphasic manner (τfast = 34 ms, τslow = 2.5 s). The faster phase of voltage-sensor return slowing correlated with the kinetics of pore opening. The slower component occurred over durations that exceeded channel activation and was consistent with voltage sensor relaxation. The S4-S5 linker mutation, G546L, impeded the faster phase of voltage sensor stabilization without attenuating the slower phase, suggesting that the S4-S5 linker is important for communications between the pore gate and the voltage sensor during deactivation. These data also demonstrate that the mechanisms of pore gate-opening-induced and relaxation-induced voltage-sensor stabilization are separable. Deletion of the distal N-terminus (Δ2-135) accelerated off-gating current, but did not influence the relative contribution of either mechanism of stabilization of the voltage sensor. Lastly, we characterized mode-shift behavior in hERG channels, which results from stabilization of activated channel states. The apparent mode-shift depended greatly on recording conditions. By measuring slow activation and deactivation at steady state we found the "true" mode-shift to be ∼15 mV. Interestingly, the "true" mode-shift of gating currents was ∼40 mV, much greater than that of the pore gate. This demonstrates that voltage sensor return is less energetically favorable upon repolarization than pore gate closure. We interpret this to indicate that stabilization of the activated voltage sensor limits the return of hERG channels to rest. The data suggest that this stabilization occurs as a result of reconfiguration of the pore gate upon opening by a mechanism that is influenced by the S4-S5 linker, and by a separable voltage-sensor intrinsic relaxation mechanism.


Assuntos
Fenômenos Eletrofisiológicos , Canais de Potássio Éter-A-Go-Go/química , Canais de Potássio Éter-A-Go-Go/metabolismo , Potenciais da Membrana , Canais de Potássio Éter-A-Go-Go/genética , Humanos , Ativação do Canal Iônico , Cinética , Mutação , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Porosidade , Estabilidade Proteica
5.
Mol Pain ; 13: 1744806917748051, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29212403

RESUMO

Chemical calcium indicators have been commonly used to monitor calcium (Ca2+) activity in cell bodies, i.e., somata, of isolated dorsal root ganglion neurons. Recent studies have shown that dorsal root ganglion somata play an essential role in soma-glia interactions and actively participate in the transmission of nociceptive signals. It is therefore desirable to develop methods to study Ca2+ activity in neurons and glia in intact dorsal root ganglia. In our previous studies, we found that incubation of intact dorsal root ganglia with acetoxymethyl dye resulted in efficient Ca2+ dye loading into glial cells but limited dye loading into neurons. Here, we introduce a useful method to load Ca2+ dyes in intact dorsal root ganglion neurons through electroporation. We found that electroporation greatly facilitated loading of Fluo-4 acetoxymethyl, Oregon green bapta-1-488 acetoxymethyl, and Fluo-4 pentapotassium salt into dorsal root ganglion neurons. In contrast, electroporation did not further facilitate dye loading into glia. Using electroporation followed by incubation of acetoxymethyl form Ca2+ dye, we can load acetoxymethyl Ca2+ dye well in both neurons and glia. With this approach, we found that inflammation induced by complete Freund's adjuvant significantly increased the incidence of neuron-glia interactions in dorsal root ganglia. We also confirmed the actions of capsaicin and morphine on Ca2+ responses in dorsal root ganglion neurons. Thus, by promoting the loading of Ca2+ dye in neurons and glia through electroporation and incubation, Ca2+ activities in neurons and neuron-glia interactions can be well studied in intact dorsal root ganglia.


Assuntos
Cálcio/metabolismo , Eletroporação/métodos , Corantes Fluorescentes/metabolismo , Gânglios Espinais/metabolismo , Neurônios/metabolismo , Compostos de Anilina/metabolismo , Animais , Dextranos , Estimulação Elétrica , Inflamação/patologia , Masculino , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Neurônios/efeitos dos fármacos , Dor/metabolismo , Dor/patologia , Cloreto de Potássio/farmacologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Xantenos/metabolismo
6.
Int J Dent Hyg ; 14(2): 82-91, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25759177

RESUMO

OBJECTIVES: Stroke survivors experience poor oral health when discharged from the hospital to the community. The aim of this study was to evaluate the effectiveness of a home-based oral care training programme on knowledge, attitude, self-efficacy and practice behaviour of family caregivers. METHODS: A randomized controlled trial was conducted. The experimental group consisted of 48 family caregivers who received the home-based oral care training programme, and the control group consisted of 46 family caregivers who received routine oral care education. The outcomes were measured by the Knowledge of Oral Care, Attitude towards Oral Care, Self-Efficacy of Oral Care and Behaviour of Oral Care before the training programme, and at one and two months afterwards. The data were analysed using mixed model anova to determine differences in the outcomes between the two groups. RESULTS: The findings demonstrated that the intervention group had more knowledge (t = 8.80, P < 0. 001), greater self-efficacy (t = 3.53, P < 0.01) and better oral care behaviour (t = 11.93, P < 0.001) than the control group at one and two months, with statistically significant differences in oral care knowledge, self-efficacy and behaviour outcome over time. The attitude of the intervention group towards oral care practice was generally positive (mean of baseline and two month = 12.9 and 14.7), but no significant difference in attitude change between the control and intervention groups (t = 1.56, P = 0.12). The treatment interaction effect was significant for the family caregivers' behaviour of oral care at one and two months of the intervention for both groups. CONCLUSION: Our individualized home-based oral care education can achieve significant improvements in oral care knowledge and self-efficacy among family caregivers of stroke survivors, and it can sufficiently empower them to modify their oral care practices in a home-based healthcare environment.


Assuntos
Cuidadores , Saúde Bucal , Autoeficácia , Acidente Vascular Cerebral/enfermagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Sobreviventes
7.
Community Dent Health ; 32(3): 137-42, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26513847

RESUMO

OBJECTIVE: To evaluate the effectiveness of home-based oral care training programs on tongue coating (TC), dental plaque (DP), and symptoms of respiratory infection (SRI) in stroke survivors. METHODS: A single-blind, randomised, controlled trial conducted in a home-based setting over 2 months. Stroke survivors (n=48, experimental group) and their family caregivers received home-based oral care training programme while a control group of 46 stroke survivors and family caregivers received routine oral care education with swabs. TC, DP, and SRI were assessed at baseline and after one and two months, with results analysed using Mixed Model ANOVA. RESULTS: Poor oral hygiene and overall neglect of home oral care practices were observed at baseline. TC and DP scores were significantly reduced in the experimental group receiving the home-base oral care training program compared to the control group, who received only routine oral care education (P<0.001). The groupxtime interaction was significant, with decreased TC and DP scores for both groups at one month and at two months of additional care (when compared to baseline). The SRI scores were not significantly different between groups (P>0.05). The groupxtime interaction did not correlate with SRI for either group when compared to the baseline and to one month and two months of additional care. No adverse events were encountered and there was no external funding. CONCLUSIONS: Home-based oral care training programme had a beneficial effect on oral health as measured by TC and DP scores. The effect on SRI requires further longitudinal study.


Assuntos
Cuidadores/educação , Educação em Saúde Bucal , Assistência Domiciliar/métodos , Higiene Bucal , Acidente Vascular Cerebral/enfermagem , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Método Simples-Cego , Taiwan
8.
Biophys J ; 106(5): 1057-69, 2014 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-24606930

RESUMO

In Shaker-like channels, the activation gate is formed at the bundle crossing by the convergence of the inner S6 helices near a conserved proline-valine-proline motif, which introduces a kink that allows for electromechanical coupling with voltage sensor motions via the S4-S5 linker. Human ether-a-go-go-related gene (hERG) channels lack the proline-valine-proline motif and the location of the intracellular pore gate and how it is coupled to S4 movement is less clear. Here, we show that proline substitutions within the S6 of hERG perturbed pore gate closure, trapping channels in the open state. Performing a proline scan of the inner S6 helix, from Ile(655) to Tyr(667) revealed that gate perturbation occurred with proximal (I655P-Q664P), but not distal (R665P-Y667P) substitutions, suggesting that Gln(664) marks the position of the intracellular gate in hERG channels. Using voltage-clamp fluorimetry and gating current analysis, we demonstrate that proline substitutions trap the activation gate open by disrupting the coupling between the voltage-sensing unit and the pore of the channel. We characterize voltage sensor movement in one such trapped-open mutant channel and demonstrate the kinetics of what we interpret to be intrinsic hERG voltage sensor movement.


Assuntos
Substituição de Aminoácidos , Canais de Potássio Éter-A-Go-Go/química , Canais de Potássio Éter-A-Go-Go/metabolismo , Espaço Intracelular/metabolismo , Ativação do Canal Iônico , Prolina , Motivos de Aminoácidos , Animais , Transporte de Elétrons , Canais de Potássio Éter-A-Go-Go/genética , Humanos , Modelos Moleculares , Porosidade , Xenopus/genética
9.
Gene Ther ; 21(10): 888-96, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25077772

RESUMO

Mutant Kras (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is observed in more than 20% of non-small-cell lung cancers; however, no effective Kras target therapy is available at present. The Kras DNA vaccine may represent as a novel immunotherapeutic agent in lung cancer. In this study, we investigated the antitumor efficacy of the Kras DNA vaccine in a genetically engineered inducible mouse lung tumor model driven by Kras(G12D). Lung tumors were induced by doxycycline, and the therapeutic effects of Kras DNA vaccine were evaluated with delivery of Kras(G12D) plasmids. Mutant Kras(G12D) DNA vaccine significantly decreased the tumor nodules. A dominant-negative mutant Kras(G12D)N17, devoid of oncogenic activity, achieved similar therapeutic effects. The T-helper 1 immune response was enhanced in mice treated with Kras DNA vaccine. Splenocytes from mice receiving Kras DNA vaccine presented an antigen-specific response by treatment with peptides of Kras but not Hras or OVA. The number of tumor-infiltrating CD8(+) T cells increased after Kras vaccination. In contrast, Kras DNA vaccine was not effective in the lung tumor in transgenic mice, which was induced by mutant L858R epidermal growth factor receptor. Overall, these results indicate that Kras DNA vaccine produces an effective antitumor response in transgenic mice, and may be useful in treating lung cancer-carrying Ras mutation.


Assuntos
Neoplasias Pulmonares/terapia , Neoplasias Experimentais/induzido quimicamente , Proteínas Proto-Oncogênicas p21(ras)/genética , Vacinas de DNA/administração & dosagem , Animais , Doxiciclina , Vetores Genéticos/administração & dosagem , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/imunologia , Camundongos , Camundongos Transgênicos , Terapia de Alvo Molecular , Mutação , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/terapia , Plasmídeos/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Vacinas de DNA/farmacologia
10.
Eur J Clin Microbiol Infect Dis ; 33(4): 591-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24136062

RESUMO

A contaminated hospital environment has been identified as an important reservoir of pathogens causing healthcare-associated infections. This study is to evaluate the efficacy of bacteria killing nanotechnology Bio-Kil on reducing bacterial counts in an intensive care unit (ICU). Two single-bed rooms (S-19 and S-20) in the ICU were selected from 7 April to 27 May 2011. Ten sets of new textiles (pillow cases, bed sheets, duvet cover, and patient clothing) used by patients in the two single-bed rooms were provided by the sponsors. In the room S-20, the 10 sets of new textiles were washed with Bio-Kil; the room walls, ceiling, and air-conditioning filters were treated with Bio-Kil; and the surfaces of instruments (respirator, telephone, and computer) were covered with Bio-Kil-embedded silicon pads. Room S-19 served as the control. We compared the bacterial count on textiles and environment surfaces as well as air samples between the two rooms. A total of 1,364 samples from 22 different sites in each room were collected. The mean bacterial count on textiles and environmental surfaces in room S-20 was significantly lower than that in room S-19 (10.4 vs 49.6 colony-forming units [CFU]/100 cm(2); P < 0.001). Room S-20 had lower bacterial counts in air samples than room S-19 (33.4-37.6 vs 21.6-25.7 CFU/hour/plate; P < 0.001). The density of microbial isolations was significantly greater among patients admitted to room S-19 than those to room S-20 (9.15 vs 5.88 isolates per 100 patient-days, P < 0.05). Bio-Kil can significantly reduce bacterial burden in the environment of the ICU.


Assuntos
Controle de Infecções/métodos , Unidades de Terapia Intensiva , Nanotecnologia/métodos , Esterilização/métodos , Contagem de Colônia Microbiana , Humanos , Esterilização/instrumentação
11.
Glia ; 61(10): 1571-81, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23918214

RESUMO

Studies of the structural organization and functions of the cell body of a neuron (soma) and its surrounding satellite glial cells (SGCs) in sensory ganglia have led to the realization that SGCs actively participate in the information processing of sensory signals from afferent terminals to the spinal cord. SGCs use a variety ways to communicate with each other and with their enwrapped soma. Changes in this communication under injurious conditions often lead to abnormal pain conditions. "What are the mechanisms underlying the neuronal soma and SGC communication in sensory ganglia?" and "how do tissue or nerve injuries affect the communication?" are the main questions addressed in this review.


Assuntos
Comunicação Celular/fisiologia , Gânglios Sensitivos/citologia , Neuroglia/fisiologia , Neurônios/fisiologia , Animais
12.
Br J Cancer ; 108(11): 2241-9, 2013 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-23674086

RESUMO

BACKGROUND: We demonstrated how to comprehensively translate the existing and updated scientific evidence on genomic discovery, tumour phenotype, clinical features, and conventional risk factors in association with breast cancer to facilitate individually tailored screening for breast cancer. METHODS: We proposed an individual-risk-score-based approach that translates state-of-the-art scientific evidence into the initiators and promoters affecting onset and subsequent progression of breast tumour underpinning a novel multi-variable three-state temporal natural history model. We applied such a quantitative approach to a population-based Taiwanese women periodical screening cohort. RESULTS: Risk prediction for pre-clinical detectable and clinical-detected breast cancer was made by the two risk scores to stratify the underlying population to assess the optimal age to begin screening and the inter-screening interval for each category and to ascertain which high-risk group requires an alternative image technique. The risk-score-based approach significantly reduced the interval cancer rate as a percentage of the expected rate in the absence of screening by 30% and also reduced 8.2% false positive cases compared with triennial universal screening. CONCLUSION: We developed a novel quantitative approach following the principle of translational research to provide a roadmap with state-of-the-art genomic discovery and clinical parameters to facilitate individually tailored breast cancer screening.


Assuntos
Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer/métodos , Medicina de Precisão/métodos , Fatores Etários , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Estatísticos , Fenótipo , Medicina de Precisão/estatística & dados numéricos , Valor Preditivo dos Testes , Fatores de Risco
13.
Br J Dermatol ; 168(5): 1054-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23330740

RESUMO

BACKGROUND: While the chronic inflammation related to autoimmune diseases is known to be associated with an increased cardiovascular risk, much less is known about cerebrovascular risks. OBJECTIVES: The present population-based, age- and sex-matched follow-up study was undertaken to investigate the risks of acute myocardial infarction (AMI) and ischaemic stroke in patients with dermatomyositis (DMS). METHODS: In total 907 patients with DMS were enrolled and compared with a non-DMS control group consisting of 4535 age- and sex-matched, randomly sampled subjects without DMS. The AMI-free and ischaemic stroke-free survival curves were generated using the Kaplan-Meier method. Cox proportional hazard regression was used to estimate the DMS-associated risks of AMI and ischaemic stroke. RESULTS: During the 2-year follow-up period, 14 patients with DMS (1.5%) and 18 patients in the non-DMS control group (0.4%) suffered AMIs. The crude hazard ratio (HR) for suffering an AMI in patients with DMS compared with subjects in the non-DMS group was 3.96 [95% confidence interval (CI) 1.97-7.96, P = 0.0001], while the adjusted HR was 3.37 (95% CI 1.67-6.80, P = 0.0007), after taking into account demographic characteristics and cardiovascular comorbidities. During the same follow-up period, 46 patients (5.1%) and 133 subjects in the control group (2.9%) developed ischaemic strokes. The crude HR for developing an ischaemic stroke in patients with DMS compared with subjects in the non-DMS group was 1.78 (95% CI 1.27-2.49, P = 0.0007), and the adjusted HR was 1.67 (95% CI, 1.19-2.34, P = 0.0028). CONCLUSIONS: These findings suggest that DMS is associated with an increased risk of cardiovascular and cerebrovascular events.


Assuntos
Doenças Cardiovasculares/etiologia , Dermatomiosite/complicações , Acidente Vascular Cerebral/etiologia , Adulto , Idoso , Povo Asiático , Doenças Cardiovasculares/epidemiologia , Dermatomiosite/epidemiologia , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Taiwan/epidemiologia
14.
Br Dent J ; 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37041240

RESUMO

Introduction This study looks at the amount of oral medicine activity in oral and maxillofacial surgery (OMFS) units in both South East Wales and South West England, and to consider the development of training programmes in oral medicine and OMFS, to determine how to best deliver a service which would benefit patients with oral medicine diagnoses.Materials and methods Following institutional approvals, local OMFS units in South East Wales and South West England collected data from OMFS outpatient clinics to determine what proportion of patient diagnoses fell within the scope of practice of oral medicine.Results In South East Wales in 2017, patients with oral medicine diagnoses formed 45% of total outpatient activity in OMFS outpatient clinics compared to 37% of patients in the South West of England in 2021. Patients with oral medicine diagnoses were predominantly female and in the older age groups.Discussion and conclusions Changing age demographics suggest that the demand for specialist oral medicine services will continue to rise. Outside of the university dental hospital setting, where all UK oral medicine units are currently located, there is a growing need for specialists in oral medicine to work alongside colleagues in OMFS in district general hospitals to provide specialist oral medicine care to an increasingly large and complex patient group, ideally as part of a managed clinical network.

15.
J Air Waste Manag Assoc ; 62(1): 92-102, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22393814

RESUMO

This study determines whether environment-protecting pervious pavement can dilute pollutants immediately after emissions from vehicle. The turbulence-driven dry-deposition process is too slow to be considered in this aspect. The pavement used is the JW pavement (according to its inventors name), a high-load-bearing water-permeable pavement with patents in over 100 countries, which has already been used for more than 8 years in Taiwan and is well suited to replacing conventional road pavement, making the potential implementation of the study results feasible. The design of this study included two sets of experiments. Variation of the air pollutant concentrations within a fenced area over the JW pavement with one vehicle discharging emissions into was monitored and compared with results over a non-JW pavement. The ambient wind speed was low during the first experiment, and the results obtained were highly credible. It was found that the JW pavement diluted vehicle pollutant emissions near the ground surface by 40%-87% within 5 min of emission; whereas the data at 2 m height suggested that about 58%-97% of pollutants were trapped underneath the pavement 20 min after emission. Those quantitative estimations may be off by +/- 10%, if errors in emissions and measurements were considered. SO2 and CO2 underwent the most significant reduction. Very likely, pollutants were forced to move underneath due to the special design of the pavement. During the second experiment, ambient wind speeds were high and the results obtained had less credibility, but they did not disprove the pollutant dilution capacity of the JW pavement. In order to track the fate of pollutants, parts of the pavement were removed to reveal a micro version of wetland underneath, which could possibly hold the responsibility of absorbing and decomposing pollutants to forms harmless to the environment and human health.


Assuntos
Poluentes Atmosféricos/química , Materiais de Construção , Monitoramento Ambiental/métodos , Veículos Automotores , Emissões de Veículos/análise , Dióxido de Carbono/química , Monóxido de Carbono/química , Óxidos de Nitrogênio/química , Ozônio/química , Dióxido de Enxofre/química , Fatores de Tempo
16.
Gene Ther ; 18(4): 372-83, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21107437

RESUMO

The transcription factor Forkhead box O3 (Foxo3) has a critical role in suppressing the expansion of antigen-specific effector T-cell populations; hence, Foxo3 is a potential target for enhancing the antitumor immunity of cancer vaccines. In this report, we evaluated the potential of RNA interference (RNAi)-mediated silencing of Foxo3 in antigen-presenting cells as an adjuvant for HER2/neu DNA cancer vaccines. Bicistronic plasmids expressing the N-terminal extracellular domain of human HER-2/neu and the Foxo3 short hairpin RNA (hN'-neu-Foxo3 shRNA) or the scrambled control (hN'-neu-scramble shRNA) were subcutaneously injected into mice by gene gun administration to elicit antitumor immunity against p185neu-overexpressing MBT-2 bladder tumor cells. We found that mice treated with hN'-neu-Foxo3 shRNA showed greater reductions in tumor growth and longer survival times than mice treated with hN'-neu-scramble shRNA, indicating that the silencing of Foxo3 enhanced the antitumor efficacy of the HER-2/neu cancer vaccine. Cytotoxicity analyses further revealed that the Foxo3 shRNA-enhanced antitumor effect was associated with significant increases in the number of functional CD8(+) T cells and in the levels of cytotoxic T lymphocytes activity. Interleukin-6 was induced by hN'-neu-Foxo3 shRNA treatment but did not have a critical role in the antitumor effect of the hN'-neu-Foxo3 shRNA vaccine. Moreover, in vivo lymphocyte depletion analyses confirmed that the antitumor efficacy of the hN'-neu-Foxo3 shRNA vaccine depended on functional CD8(+) T cells. Finally, Foxo3 suppression was shown to markedly improve the effect of the HER-2/neu DNA vaccine in limiting the growth and lung metastases of MBT-2 cells. Overall, these results support RNAi-mediated silencing of Foxo3 as an effective strategy to enhance the therapeutic antitumor effect of HER-2/neu DNA vaccines against p185neu-positive tumors.


Assuntos
Células Apresentadoras de Antígenos/metabolismo , Vacinas Anticâncer/imunologia , Fatores de Transcrição Forkhead/genética , Genes erbB-2 , Interferência de RNA , Vacinas de DNA/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Biolística , Linhagem Celular , Chlorocebus aethiops , Células Dendríticas/imunologia , Proteína Forkhead Box O3 , Vetores Genéticos , Humanos , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/farmacologia , Linfócitos T/imunologia , Neoplasias da Bexiga Urinária/prevenção & controle
19.
Eur J Gynaecol Oncol ; 31(4): 402-10, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20882882

RESUMO

INTRODUCTION: Ovarian cancer is of worldwide importance, and has a significantly high mortality rate due to therapy failure. Drug resistance might be one of most importance factors. Histone deacetylase inhibitors (HDACi) have been reported to be a new class of promising anti-tumor agents, thus this study aimed to investigate the effect of HDAC on the chemo-resistance genes of human ovarian carcinoma cell lines. METHODS: The expressions of ATP binding cassette (ABC) transporter genes, multidrug-resistant protein (MDR1) and multidrug resistance-associated proteins (MRP1 and 2) of ovarian cancer cell lines OC-109 and SK-OV-3 after HDACi treatment were determined. RESULTS: HDACi, including sodium butyrate (NaB), suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) reduced ovarian cancer cell viability from 4.4% to 68.8%, in both dose- and time-dependent manners. The effect of HDACi on MDR1, MRP1, and MRP2 showed induced expression of MDR1 mRNA, but reduced mRNA expression of MRP1 and MRP2. CONCLUSIONS: The effect of HDACi on the reduced viability of ovarian cancer cell lines, concomitant with the induced expression of MDR1 and reduced expression of MRP1 and 2, might provide additional benefits in the management of ovarian cancers in the future.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Antineoplásicos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Butiratos/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Ácidos Hidroxâmicos/farmacologia , Neoplasias Ovarianas/patologia
20.
BMJ Case Rep ; 13(8)2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32816941

RESUMO

This case describes the successful pulmonary rehabilitation of a premorbidly independent female in the early 80s who was admitted for acute respiratory distress syndrome secondary to COVID-19 requiring 14 days of intubation. Patient was admitted to the acute rehabilitation unit 1 month after hospitalisation. Patient initially had poor endurance and was only able to ambulate with a front wheel walker for 150 feet, and also had tachycardia and decreased oxygen saturation after ambulation. During patient's rehabilitation course, therapy was focused on improving activity tolerance. Ten days after admission, patient was able to ambulate without an assistive device for 250 feet and with a rollator for over 900 feet. Patient also showed improvement in gait speed, heart rate, oxygen saturation after ambulation and incentive spirometer volume. This case demonstrates that pulmonary rehabilitation is an important component of inpatient care for patients with COVID-19 to improve functional exercise capacity and aerobic capacity.


Assuntos
Betacoronavirus , Infecções por Coronavirus/reabilitação , Pneumonia Viral/reabilitação , Síndrome do Desconforto Respiratório/reabilitação , Terapia Respiratória/métodos , Cuidados Semi-Intensivos/métodos , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Recuperação de Função Fisiológica , Síndrome do Desconforto Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório/virologia , SARS-CoV-2 , Resultado do Tratamento , Caminhada
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