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AIM: To evaluate the clinical and cost implications of using computed tomography colonography (CTC) compared to optical colonoscopy (OC) as the initial colonic investigation in patients with low-to-intermediate risk of colorectal cancer (CRC). MATERIALS AND METHODS: A non-randomised, prospective single-centre study recruited 180 participants to compare the cost implications of two clinical pathways used in the diagnosis of low-to-intermediate risk of CRC that differ in the initial diagnostic test, either CTC or OC. Costs were compared using generalised linear models (GLM) and combined with quality-adjusted life years (QALYs, based on the EQ-5D-5L) to estimate cost-effectiveness at 6 months post-recruitment. Secondary outcomes assessed access to care and patient satisfaction. RESULTS: Mean (SD, n) cost at 6 months post-recruitment per participant was £991 (£316, n=105) for the OC group and £645 (£607, n=68) for the CTC group, leading to an estimated cost difference of -£370 (95% CI: -£554, -£185, p<0.001). Assuming a £20,000 willingness-to-pay per QALY threshold, there was a 91.4% probability of CTC being cost-effective at month 6. The utilisation of CTC led to improved access to care, with a shorter mean time from referral from primary care to results (6.3 days difference, p=0.005). No differences in patient satisfaction were detected between both groups. CONCLUSION: The utilisation of CTC as the first-line investigation for patients with low-to-intermediate risk of CRC has the potential to release OC capacity, of pivotal importance for patients more likely to benefit from an invasive diagnostic approach.
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Colonografía Tomográfica Computarizada/estadística & datos numéricos , Neoplasias Colorrectales/diagnóstico , Tamizaje Masivo/métodos , Satisfacción del Paciente , Anciano , Colonografía Tomográfica Computarizada/economía , Colonoscopía/economía , Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/economía , Análisis Costo-Beneficio , Femenino , Estudios de Seguimiento , Humanos , Masculino , Tamizaje Masivo/economía , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Family quality of life (FQOL) is a recent concept in intellectual/developmental disability research. Outcomes for the family are important to the provision of services because families, rather than institutions, are increasingly considered the primary support unit. This article presents Australian findings using the international Family Quality of Life Survey: Main Caregivers of People with Intellectual or Developmental Disabilities (FQOLS-2006). METHOD: Forty-two South Australian main caregivers of people with an intellectual/developmental disability were interviewed using the FQOLS-2006. The FQOL domains assessed were Health of the Family, Financial Well-being, Family Relationships, Support from Other People, Support from Disability-Related Services, Influence of Values, Careers, Leisure and Recreation, and Community Interaction. Domains were measured in terms of Importance, Opportunities, Attainment, Initiative, Stability and Satisfaction. The FQOLS-2006 asked about the family's practical and emotional Support from Other People together, whereas the current study separated the constructs of practical and emotional support. Questions pertaining to FQOL in the past were also added, in order to gain a broader picture of present FQOL. RESULTS: Results indicated that families considered all the FQOL domains to be important. However, Health, Family Relationships and Financial Well-being were regarded as slightly more important than Practical and Emotional Support from Others. The attainment of Family Relationships, Health, Values, and Leisure and Recreation were rated as quite a bit, but Practical Support from Other People was only rated as a little. Families were generally satisfied with all FQOL domains, but they were satisfied with their Family Relationships and they were neither satisfied or dissatisfied with their Financial Well-being. Results also indicated that there was a need to distinguish between the provision of practical and emotional support from others, because the attainment of emotional support was rated at a slightly higher level than practical support. CONCLUSIONS: The FQOLS-2006 provided a comprehensive measure of FQOL, which, with some additional modifications, could be used to better inform service provisions and ultimately enhance the quality of life of people with intellectual/developmental disabilities and their families.
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Cuidadores/psicología , Discapacidades del Desarrollo/enfermería , Personas con Discapacidad/estadística & datos numéricos , Salud de la Familia/estadística & datos numéricos , Discapacidad Intelectual/enfermería , Calidad de Vida/psicología , Adolescente , Adulto , Anciano , Australia , Niño , Preescolar , Costo de Enfermedad , Comparación Transcultural , Discapacidades del Desarrollo/psicología , Familia/psicología , Femenino , Encuestas Epidemiológicas , Humanos , Discapacidad Intelectual/psicología , Masculino , Persona de Mediana Edad , Padres/psicología , Psicometría/instrumentación , Psicometría/métodos , Apoyo Social , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
This study determined whether targeted metabolomic profiling of serum, using 1H nuclear magnetic resonance, could be employed to distinguish the effects of obesity from those of diet in mice. Following weaning, littermates were randomly divided into two diet groups: chow and high fat. After 12 weeks of dietary manipulation, fat-fed animals were obese and hyperglycaemic. Mice from each treatment either maintained their current diet or switched to the opposite diet for a final week. Differences in metabolite levels were determined using orthogonal projection to latent structures and cross-validated discriminant analysis. The short- and long-term effects of each diet could be clearly distinguished. Short-term diet effects are the major contributor to the metabolic profile, underscoring the need for controls beyond the standard fast before serum collection. This work shows the importance of dietary controls when attempting to isolate obesity-related changes and highlights the ability of metabolomics to identify subtle changes when experiments are properly structured.
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Dieta/efectos adversos , Espectroscopía de Resonancia Magnética/métodos , Metabolómica/métodos , Obesidad/metabolismo , Animales , Masculino , Ratones , Ratones Obesos , Obesidad/diagnóstico , Distribución Aleatoria , TiempoRESUMEN
We investigated the effect of full and partial mechanical reperfusion on MMP-9 expression in rat brain following middle cerebral artery occlusion, mimicking mechanical thrombectomy. Using percentage hemispheric lesion volume and oedema as measures, partial reperfusion reduced extent of brain damage caused by MCA occlusion, but the protective effect was less pronounced than with complete reperfusion. Using ELISA quantification in fresh frozen tissue, confirmed by immunofluorescence in perfusion fixed tissue, increased MMP-9 expression was observed in infarcted tissue. MMP-9 was increased in lesioned tissue of the anterior and posterior temporal cortex and underlying striatal tissue, but also the normal appearing frontal cortex. No significant increase in MMP-9 in the hippocampus was observed, nor in the unlesioned contralateral hemisphere. Both partial reperfusion and full reperfusion reduced the regional MMP expression significantly. The highest levels of MMP-9 were observed in lesioned brain regions in the non-reperfused group. MMP-9 expression was evident in microvessels and in neuronal cell bodies of affected tissue. This study shows that MMP-9 brain levels are reduced relative to the extent of reperfusion. These observations suggest targeting early increases in MMP-9 expression as a possible neuroprotective therapeutic strategy and highlight the rat MCA occlusion model as an ideal model in which to study candidate therapeutics.
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Isquemia Encefálica , Metaloproteinasa 9 de la Matriz , Daño por Reperfusión , Animales , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media , Metaloproteinasa 9 de la Matriz/metabolismo , Ratas , ReperfusiónRESUMEN
BACKGROUND: Prescription methadone or buprenorphine enables people with opioid use disorder to stop heroin use safely while avoiding withdrawal. To ensure methadone is taken as prescribed and to prevent diversion onto the illicit market, people starting methadone take their daily dose under a pharmacist's supervision. Many patients miss their daily methadone dose risking withdrawal, craving for heroin and overdose due to loss of heroin tolerance. Contingency management (CM) can improve medication adherence, but remote delivery using technology may be resource-light and cost-effective. We developed an innovative way to deliver CM by mobile telephone. Software monitors patients' attendance and supervised methadone consumption through an internet self-login at the pharmacy and sends reinforcing text messages to patients' mobile telephones. A linked system sends medication adherence reports to prescribers and provides early warning alerts of missed doses. A pre-paid debit card system provides financial incentives. METHODS: A cluster randomised controlled trial design was used to test the feasibility of conducting a future trial of mobile telephone CM to encourage adherence to supervised methadone in community pharmacies. Each cluster (drug service/3 allied pharmacies) was randomly allocated to provide patient's presenting for a new episode of opiate agonist treatment (OAT) with either (a) mobile telephone text message CM, (b) mobile telephone text message reminders, or (c) no text messages. We assessed acceptability of the interventions, recruitment, and follow-up procedures. RESULTS: Four drug clinics were approached and three recruited. Thirty-three pharmacists were approached and 9 recruited. Over 3 months, 173 individuals were screened and 10 enrolled. Few patients presented for OAT and high numbers were excluded due to receiving buprenorphine or not attending participating pharmacies. There was 96% consistency in recording medication adherence by self-login vs. pharmacy records. In focus groups, CM participants were positive about using self-login, the text messages, and debit card. Prescribers found weekly reporting, time saving, and allowed closer monitoring of patients. Pharmacists reported that the tablet device was easy to host. CONCLUSION: Mobile telephone CM worked well, but a planned future trial will use modified eligibility criteria (existing OAT patients who regularly miss their methadone/buprenorphine doses) and increase the number of participating pharmacies. TRIAL REGISTRATION: The trial is retrospectively registered, ISRCTN 58958179 .
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BACKGROUND: The 22q11.2 deletion syndrome (22qDS) confers high risk for intellectual disability and neuropsychological/academic impairment, although a minority of patients show average intelligence. Intellectual heterogeneity and the high prevalence of psychiatric diagnoses in earlier studies may have obscured the prototypical neuropsychological profile in 22qDS. METHODS: We examined intelligence, memory, reading and mathematical processes in 31 children/adolescents with 22qDS, selected for educational underachievement and an absence of psychiatric diagnoses, using standardised, psychometrically matched instruments that specify how typical a score is for a given intelligence quotient (IQ). RESULTS: Corroborating earlier findings, verbal IQ was significantly superior to performance IQ; verbal memory and basic reading were relative strengths; and visual/spatial memory was a relative weakness. All four findings transcended performance characteristics that are typical of low-IQ individuals. Rote learning yielded the highest score; reading comprehension, numerical operations and mathematical reasoning were among the lowest-performed academic domains. Albeit in the expected direction, performance in the respective components could not be clearly differentiated from what is IQ-appropriate. CONCLUSIONS: A superiority of verbal intelligence over non-verbal intelligence, relative strengths in verbal memory and basic reading, and a relative weakness in visual/spatial memory are likely to be core characteristics of children/adolescents with 22qDS, transcending performance features that are typical of individuals with low IQ.
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Deleción Cromosómica , Cromosomas Humanos Par 22 , Inteligencia , Matemática , Memoria , Lectura , Adolescente , Niño , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Psicometría , Percepción Espacial , Rendimiento Escolar Bajo , Conducta Verbal , Percepción VisualRESUMEN
The objective of this study was to evaluate the efficacy of two non-antibiotic treatment options for digital dermatitis (DD) on an organic certified dairy farm. A randomized clinical trial was conducted using 70 multiparous Holstein cows with an early DD lesion at a USDA certified organic dairy farm in Northern Colorado, USA. Cows were enrolled in the study based on the presence of early DD lesions (scores M1 and M2) and randomly assigned to one of three treatments: (1) topical application of copper sulfate and iodine (CUI); (2) topical application of honey and iodine (HOI); and (3) control subject to no treatment (CON). Cows were evaluated at enrolment and on days 3, 12, 28, and 120 post treatment for pain and lesion size and received a locomotion and a lesion score. Cure was defined as the transition from active to non-active stages (M1/M2 to M0 or M4). The formulations had variable effects on the treatment of DD. The cure rate was numerically higher for CUI on all follow up days. The proportion of cows experiencing pain on d3 after treatment was greater in CON, followed by HOI and CUI. However, this proportion increased in HOI during the follow up period. The CUI group had a greater reduction in lesion size and larger lesions persisted in HOI. Non-antibiotic treatment formulations were partially effective in the treatment of DD in organic dairy cows: The two non-antibiotic formulations resulted in an earlier transition to mature lesions compared with the control group. The CUI combination was the most effective treatment in reducing lesion size, pain, and lameness in affected cows. However, this combination had short-term efficacy, which did not persist throughout the duration of the study. The HOI combination produced only transient reduction in lesion size.
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Enfermedades de los Bovinos/tratamiento farmacológico , Sulfato de Cobre/uso terapéutico , Dermatitis Digital/tratamiento farmacológico , Miel , Yodo/uso terapéutico , Administración Tópica , Animales , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/veterinaria , Bovinos , Colorado , Sulfato de Cobre/administración & dosificación , Industria Lechera , Femenino , Pezuñas y Garras/efectos de los fármacos , Yodo/administración & dosificación , Cojera Animal/tratamiento farmacológico , Agricultura Orgánica , Dolor , Resultado del TratamientoRESUMEN
Numerous underwater mounds found on the continental shelf of the Beaufort Sea are thought to be pingos (hills that have a central core of ice) which have formed in the marine environment subsequent to oceanic transgression.
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Experimental acidification of a small lake from an original pH value of 6.8 to 5.0 over an 8-year period caused a number of dramatic changes in the lake's food web. Changes in phytoplankton species, cessation of fish reproduction, disappearance of the benthic crustaceans, and appearance of filamentous algae in the littoral zone were consistent with deductions from synoptic surveys of lakes in regions of high acid deposition. Contrary to what had been expected from synoptic surveys, acidification of Lake 223 did not cause decreases in primary production, rates of decomposition, or nutrient concentrations. Key organisms in the food web leading to lake trout, including Mysis relicta and Pimephales promelas, were eliminated from the lake at pH values as high as 5.8, an indication that irreversible stresses on aquatic ecosystems occur earlier in the acidification process than was heretofore believed. These changes are caused by hydrogen ion alone, and not by the secondary effect of aluminum toxicity. Since no species of fish reproduced at pH values below 5.4, the lake would become fishless within about a decade on the basis of the natural mortalities of the most long-lived species.
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Twenty years of climatic, hydrologic, and ecological records for the Experimental Lakes Area of northwestern Ontario show that air and lake temperatures have increased by 2 degrees C and the length of the ice-free season has increased by 3 weeks. Higher than normal evaporation and lower than average precipitation have decreased rates of water renewal in lakes. Concentrations of most chemicals have increased in both lakes and streams because of decreased water renewal and forest fires in the catchments. In Lake 239, populations and diversity of phytoplankton also increased, but primary production showed no consistent trend. Increased wind velocities, increased transparency, and increased exposure to wind of lakes in burned catchments caused thermoclines to deepen. As a result, summer habitats for cold stenothermic organisms like lake trout and opposum shrimp decreased. Our observations may provide a preview of the effects of increased greenhouse warming on boreal lakes.
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Lameness is a multifactorial condition with many causes. In this study, cow lifetime records were used to quantify the incidence of specific lameness-causing lesions and investigate factors associated with those lesions. Of primary interest were the effects of seasonality and the effects of thin soles (TS). Thin sole-induced toe ulcers (TSTU) occurring adjacent to the white line in the apical portion of the weight-bearing surface were distinguished from white line disease (WLD) occurring in the region of the abaxial heel sole junction. Sole (SU), heel (HU), and toe (TU) ulcers; TS; sole punctures (SP); leg injuries (INJ); and other (OTH) lesions (e.g., infectious diseases, laminitis, unclassified hemorrhage) were also considered. Data were collected from May 2004 through October 2007 and included records for 4,915 cows of which 1,861 had at least one recorded lameness event. Of these, 20% were TSTU, 20% OTH, 16% SU, 13% TS, 10% WLD, 8% HU, 6% INJ, 4% SP, and 2% TU. Annual incidence risk for lameness was 49.1%. Overall incidence rate for lameness was 1.41/1,000 cow-days, and rates for all lesions were highest in the summer. As parity increased, so did incidence rates for TS, SU, WLD, HU, and INJ. For TS, TSTU, and WLD, incidence rates were lowest in early lactation (16 to 60 DIM), whereas for SU, HU, TU, incidence rates were highest in mid lactation (61 to 150 DIM). Cox proportional hazard models for TS, TSTU, WLD, SU, HU, TU, and SP included age and year of first calving and milk production capacity. Prior/concurrent lameness events, season, parity, and stage of lactation were included as time-dependent effects. Prior/concurrent TS increased the hazard for all other lesions, particularly TSTU, and HU. Having any other prior claw lesion also increased the hazard for all lesions. Hazard was highest in summer for all lesions except TU. Stage of lactation was a significant effect in hazard of TSTU, which was lowest in mid lactation (61 to 150 DIM).
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Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/patología , Industria Lechera , Enfermedades del Pie/veterinaria , Pezuñas y Garras/patología , Cojera Animal/epidemiología , Estaciones del Año , Animales , Bovinos , Femenino , Enfermedades del Pie/epidemiología , Enfermedades del Pie/patología , Incidencia , Estimación de Kaplan-Meier , Cojera Animal/patología , Modelos de Riesgos Proporcionales , Factores de Riesgo , Sudeste de Estados UnidosRESUMEN
AIMS: The aim of the Scaphoid Magnetic Resonance Imaging in Trauma (SMaRT) trial was to evaluate the clinical and cost implications of using immediate MRI in the acute management of patients with a suspected fracture of the scaphoid with negative radiographs. PATIENTS AND METHODS: Patients who presented to the emergency department (ED) with a suspected fracture of the scaphoid and negative radiographs were randomized to a control group, who did not undergo further imaging in the ED, or an intervention group, who had an MRI of the wrist as an additional test during the initial ED attendance. Most participants were male (52% control, 61% intervention), with a mean age of 36.2 years (18 to 73) in the control group and 38.2 years (20 to 71) in the intervention group. The primary outcome was total cost impact at three months post-recruitment. Secondary outcomes included total costs at six months, the assessment of clinical findings, diagnostic accuracy, and the participants' self-reported level of satisfaction. Differences in cost were estimated using generalized linear models with gamma errors. RESULTS: The mean cost up to three months post-recruitment per participant was £542.40 (sd £855.20, n = 65) for the control group and £368.40 (sd £338.60, n = 67) for the intervention group, leading to an estimated cost difference of £174 (95% confidence interval (CI) -£30 to £378; p = 0.094). The cost difference per participant increased to £266 (95% CI £3.30 to £528; p = 0.047) at six months. Overall, 6.2% of participants (4/65, control group) and 10.4% of participants (7/67, intervention group) had sustained a fracture of the scaphoid (p = 0.37). In addition, 7.7% of participants (5/65, control group) and 22.4% of participants (15/67, intervention group) had other fractures diagnosed (p = 0.019). The use of MRI was associated with higher diagnostic accuracy both in the diagnosis of a fracture of the scaphoid (100.0% vs 93.8%) and of any other fracture (98.5% vs 84.6%). CONCLUSION: The use of immediate MRI in the management of participants with a suspected fracture of the scaphoid and negative radiographs led to cost savings while improving the pathway's diagnostic accuracy and patient satisfaction. Cite this article: Bone Joint J 2019;101-B:984-994.
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Análisis Costo-Beneficio , Fracturas Óseas/diagnóstico por imagen , Costos de la Atención en Salud/estadística & datos numéricos , Imagen por Resonancia Magnética/economía , Hueso Escafoides/lesiones , Traumatismos de la Muñeca/diagnóstico por imagen , Adolescente , Adulto , Anciano , Ahorro de Costo/estadística & datos numéricos , Servicio de Urgencia en Hospital , Femenino , Estudios de Seguimiento , Fracturas Óseas/economía , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Satisfacción del Paciente/estadística & datos numéricos , Estudios Prospectivos , Radiografía , Hueso Escafoides/diagnóstico por imagen , Reino Unido , Traumatismos de la Muñeca/economía , Adulto JovenRESUMEN
Increasing duration of tamoxifen therapy improves survival in women with breast cancer but the impact of adherence to tamoxifen on mortality is unclear. This study investigated whether women prescribed tamoxifen after surgery for breast cancer adhered to their prescription and whether adherence influenced survival. A retrospective cohort study of all women with incident breast cancer in the Tayside region of Scotland between 1993 and 2002 was linked to encashed prescription records to calculate adherence to tamoxifen. Survival analysis was used to determine the effect of adherence on all-cause mortality. In all 2080 patients formed the study cohort with 1633 (79%) prescribed tamoxifen. The median duration of use was 2.42 years (IQR=1.04-4.89 years). Longer duration was associated with better survival but this varied over time. The hazard ratio for mortality in relation to duration at 2.4 years was 0.85, 95% CI=0.83-0.87. Median adherence to tamoxifen was 93% (interquartile range=84-100%). Adherence <80% was associated with poorer survival, hazard ratio 1.10, 95% CI=1.001-1.21. Persistence with tamoxifen was modest with only 49% continuing therapy for 5 years of those followed up for 5 years or more. Increased duration of tamoxifen reduces the risk of death, although one in two women do not complete the recommended 5-year course of treatment. A significant proportion of women have low adherence to tamoxifen and are at increased risk of death.
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Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Cumplimiento de la Medicación/estadística & datos numéricos , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Tamoxifeno/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
We examined the phylogenetic distribution, functionality and evolution of the sodN gene family, which has been shown to code for a unique Ni-containing isoform of superoxide dismutase (Ni-SOD) in Streptomyces. Many of the putative sodN sequences retrieved from public domain genomic and metagenomic databases are quite divergent from structurally and functionally characterized Ni-SOD. Structural bioinformatics studies verified that the divergent members of the sodN protein family code for similar three-dimensional structures and identified evolutionarily conserved amino acid residues. Structural and biochemical studies of the N-terminus 'Ni-hook' motif coded for by the putative sodN sequences confirmed both Ni (II) ligating and superoxide dismutase activity. Both environmental and organismal genomes expanded the previously noted phylogenetic distribution of sodN, and the sequences form four well-separated clusters, with multiple subclusters. The phylogenetic distribution of sodN suggests that the gene has been acquired via horizontal gene transfer by numerous organisms of diverse phylogenetic background, including both Eukaryotes and Prokaryotes. The presence of sodN correlates with the genomic absence of the gene coding for Fe-SOD, a structurally and evolutionarily distinct isoform of SOD. Given the low levels of Fe found in the marine environment from where many sequences were attained, we suggest that the replacement of Fe-SOD with Ni-SOD may be an evolutionary adaptation to reduce iron requirements.
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Biología Computacional/métodos , Evolución Molecular , Níquel/metabolismo , Streptomyces/enzimología , Superóxido Dismutasa/clasificación , Bases de Datos Genéticas , Biología Marina , Datos de Secuencia Molecular , Níquel/química , Streptomyces/genética , Homología Estructural de Proteína , Superóxido Dismutasa/química , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
The predictive ability of metabolic profiling to detect obesity-induced perturbations in metabolism has not been clearly established. Complex aetiologies interacting with environmental factors highlight the need to understand how specific manipulations alter metabolite profiles in this state. The aim of this study was to determine if targeted metabolomic profiling could be employed as a reliable tool to detect dietary-induced insulin resistance in a small subset of experimental animals (n = 10/treatment). Following weaning, male C57BL/6J littermates were randomly divided into two dietary groups: chow and high fat. Following 12 weeks of dietary manipulation, mice were fasted for 5 h prior to serum collection. The resultant high fat-fed animals were obese and insulin resistant as shown by a euglycaemic-hyperinsulinaemic clamp. Sera were analysed by proton nuclear magnetic resonance spectroscopy, and 46 known compounds were identified and quantified. Multivariate analysis by orthogonal partial least squares discriminant analysis, a projection method for class separation, was then used to establish models of each treatment. Models were able to predict class separation between diets with 90% accuracy. Variable importance plots revealed the most important metabolites in this discrimination to include lysine, glycine, citrate, leucine, suberate and acetate. These metabolites are involved in energy metabolism and may be representative of the perturbations taking place with insulin resistance. Results show metabolomics to reliably describe the metabolic effects of insulin resistance in a small subset of samples and are an initial step in establishing metabolomics as a tool to understand the biochemical signature of insulin resistance.
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Grasas de la Dieta/efectos adversos , Resistencia a la Insulina , Tejido Adiposo/metabolismo , Animales , Grasas de la Dieta/farmacología , Glucosa/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Nutrigenómica , Obesidad/metabolismo , Distribución Aleatoria , Aumento de PesoRESUMEN
BACKGROUND: Ischaemic stroke is often complicated with haemorrhage within the infarct zone or in a remote location especially when treated with intravenous thrombolysis and/or thrombectomy. While these early recanalisation treatments are highly effective, some of the benefit is lost because of haemorrhagic complications and consequential neurological deterioration of the patients. A number of mechanisms have been described that mediate the haemorrhagic changes and several agents have been tested in experimental models for inhibiting post-stroke haemorrhage. METHODS: Here, we review and discuss the small animal models of focal cerebral ischaemia and postischaemic stroke haemorrhagic transformation and how these models can best be utilised for developing further insights as well as potential treatment approaches for this serious clinical complication. RESULTS: The need to use appropriate animal models with relevant stroke risk factors to improve the clinical relevance and applicability of findings is becoming ever more apparent. Current focal ischaemia models can be adapted for the study of haemorrhagic transformation post-stroke. CONCLUSION: A number of factors can be added to the animal model design to increase the incidence and/or severity of haemorrhagic transformation post-ischaemic stroke, which can improve clinical relevance, aid the study of the pathophysiology and the future development of novel interventions.
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Isquemia Encefálica/etiología , Hemorragias Intracraneales/etiología , Accidente Cerebrovascular/etiología , Animales , Isquemia Encefálica/fisiopatología , Isquemia Encefálica/terapia , Modelos Animales de Enfermedad , Humanos , Hemorragias Intracraneales/fisiopatología , Hemorragias Intracraneales/terapia , Factores de Riesgo , Especificidad de la Especie , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/terapia , Trombectomía/efectos adversos , Terapia Trombolítica/efectos adversos , Factores de Tiempo , Tiempo de TratamientoRESUMEN
Since the first report of bovine digital dermatitis (DD) in 1974, there is a large body of the literature published; however, effective prevention and control of the disease remain elusive. Although many aspects of the pathogenesis of DD have been investigated, even some of the most basic questions such as the aetiology of this disease remain under debate. Treponema spp. have been strongly associated with DD lesions and occur in abundance in advanced lesions; however, efforts to induce disease with pure cultures of these organisms have been largely underwhelming and inconsistent. Furthermore, although the disease has been presented for several decades, there is limited scientific evidence regarding effective treatment of DD. Apparent discrepancies between effectiveness in vitro and in vivo have challenged the scientific community to identify new potential treatment options. With no treatment resulting in a 100% cure rate, the current expectation is manageable control, but prospects for the eradication of the disease are unlikely using current approaches. In order to develop more effective approaches to control DD on-farm, there is a critical need for a deeper understanding regarding the causation, ecology, transmission and treatment of this disease. In this article, we attempt to provide insights into specific research needs related to DD in order to assist the industry, researchers, pharmaceutical companies and research sponsors with decision-making and identified research gaps.
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Enfermedades de los Bovinos/prevención & control , Dermatitis Digital/prevención & control , Infecciones por Treponema/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/microbiología , Dermatitis Digital/microbiología , Treponema/patogenicidad , Infecciones por Treponema/microbiología , Infecciones por Treponema/prevención & controlRESUMEN
There are approximately 256,000 heroin and other opiate users in England of whom 155,000 are in treatment for heroin (or opiate) addiction. The majority of people in treatment receive opiate substitution treatment (OST) (methadone and buprenorphine). However, OST suffers from high attrition and persistent heroin use even whilst in treatment. Contingency management (CM) is a psychological intervention based on the principles of operant conditioning. It is delivered as an adjunct to existing evidence based treatments to amplify patient benefit and involves the systematic application of positive reinforcement (financial or material incentives) to promote behaviours consistent with treatment goals. With an international evidence base for CM, NICE recommended that CM be implemented in UK drug treatment settings alongside OST to target attendance and the reduction of illicit drug use. While there was a growing evidence base for CM, there had been no examination of its delivery in UK NHS addiction services. The PRAISe trial evaluates the feasibility, acceptability, clinical and cost effectiveness of CM in UK addiction services. It is a cluster randomised controlled effectiveness trial of CM (praise and financial incentives) targeted at either abstinence from opiates or attendance at treatment sessions versus no CM among individuals receiving OST. The trial includes an economic evaluation which explores the relative costs and cost effectiveness of the two CM intervention strategies compared to TAU and an embedded process evaluation to identify contextual factors and causal mechanisms associated with variations in outcome. This study will inform UK drug treatment policy and practice. Trial registration ISRCTN 01591254.
Asunto(s)
Terapia Conductista/métodos , Buprenorfina/administración & dosificación , Dependencia de Heroína , Servicios de Salud Mental , Metadona/administración & dosificación , Trastornos Relacionados con Opioides , Refuerzo en Psicología , Adulto , Análisis por Conglomerados , Abuso de Medicamentos/prevención & control , Abuso de Medicamentos/psicología , Femenino , Dependencia de Heroína/psicología , Dependencia de Heroína/terapia , Humanos , Masculino , Administración del Tratamiento Farmacológico/organización & administración , Administración del Tratamiento Farmacológico/normas , Servicios de Salud Mental/economía , Servicios de Salud Mental/organización & administración , Servicios de Salud Mental/normas , Antagonistas de Narcóticos/administración & dosificación , Trastornos Relacionados con Opioides/psicología , Trastornos Relacionados con Opioides/terapia , Mejoramiento de la Calidad , Reino UnidoRESUMEN
OBJECTIVE: To determine the accuracy and acceptability of a handheld scale prototype designed for nonliterate users to classify newborns into three weight categories (>or=2,500 g; 2,000 to 2,499 g; and <2,000 g). STUDY DESIGN: Weights of 1,100 newborns in Uttar Pradesh, India, were measured on the test scale and validated against a gold standard. Mothers, family members and community health stakeholders were interviewed to assess the acceptability of the test scale. RESULT: The test scale was highly sensitive and specific at classifying newborn weight (normal weight: 95.3 and 96.3%, respectively; low birth weight: 90.4 and 99.2%, respectively; very low birth weight: 91.7 and 98.4%, respectively). It was the overall agreement of the community that the test scale was more practical and easier to interpret than the gold standard. CONCLUSION: The BIRTHweigh III scale accurately identifies low birth weight and very low birth weight newborns to target weight-specific interventions. The scale is extremely practical and useful for resource-poor settings, especially those with low levels of literacy.
Asunto(s)
Peso al Nacer , Recién Nacido/fisiología , Pesos y Medidas , Agentes Comunitarios de Salud , Diseño de Equipo , Humanos , India , Recién Nacido de Bajo Peso , Población Rural , Sensibilidad y EspecificidadRESUMEN
Traumatic lesions of the sole are a common cause of lameness in beef and dairy cattle. This article provides a brief description of traumatically induced conditions with specific attention to underlying causes, treatment, and prevention. Lameness, traumatic lesions of the sole, sole punctures, thin soles, thin sole toe ulcers, toe tip necrosis syndrome, and toe abscesses are discussed.