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1.
BMC Med Educ ; 23(1): 829, 2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37924033

RESUMEN

BACKGROUND: The Covid-19 pandemic has resulted in many student populations learning online in lockdown. While the mental health consequences of lockdown are increasingly understood, the core features of 'cabin fever' - the experience of lockdown - are poorly described. METHODS: We conducted a questionnaire survey of 649 undergraduate medicine and health sciences students. Item content was developed based on current literature and input from student representatives. RESULTS: Mokken scaling identified seven questions that together formed a strongly unidimensional scale which comprised two domains: social isolation/cabin fever and demotivation / demoralisation. Scale scores were significantly associated with depression, self-rated mental health, impaired study efficacy and doomscrolling. CONCLUSIONS: The adverse effects of lockdown on student wellbeing appear to be driven to an important extent by an experience of isolation and demotivation that corresponds to narrative descriptions of cabin fever. In the foreseeable event of future pandemics, these experiences are a promising target for health promotion in students studying in lockdown.


Asunto(s)
COVID-19 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Pandemias , Estudiantes , COVID-19/epidemiología , Fiebre
2.
Mol Ther ; 29(6): 2041-2052, 2021 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-33609732

RESUMEN

Oligonucleotide therapies offer precision treatments for a variety of neurological diseases, including epilepsy, but their deployment is hampered by the blood-brain barrier (BBB). Previous studies showed that intracerebroventricular injection of an antisense oligonucleotide (antagomir) targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in animal models of epilepsy. In this study, we used assays of serum protein and tracer extravasation to determine that BBB disruption occurring after status epilepticus in mice was sufficient to permit passage of systemically injected Ant-134 into the brain parenchyma. Intraperitoneal and intravenous injection of Ant-134 reached the hippocampus and blocked seizure-induced upregulation of miR-134. A single intraperitoneal injection of Ant-134 at 2 h after status epilepticus in mice resulted in potent suppression of spontaneous recurrent seizures, reaching a 99.5% reduction during recordings at 3 months. The duration of spontaneous seizures, when they occurred, was also reduced in Ant-134-treated mice. In vivo knockdown of LIM kinase-1 (Limk-1) increased seizure frequency in Ant-134-treated mice, implicating de-repression of Limk-1 in the antagomir mechanism. These studies indicate that systemic delivery of Ant-134 reaches the brain and produces long-lasting seizure-suppressive effects after systemic injection in mice when timed with BBB disruption and may be a clinically viable approach for this and other disease-modifying microRNA therapies.


Asunto(s)
Antagomirs/genética , Barrera Hematoencefálica/metabolismo , Epilepsia/genética , Epilepsia/terapia , Animales , Antagomirs/administración & dosificación , Barrera Hematoencefálica/patología , Manejo de la Enfermedad , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Regulación de la Expresión Génica , Silenciador del Gen , Técnicas de Transferencia de Gen , Predisposición Genética a la Enfermedad , Terapia Genética , Ratones , MicroARNs/genética , Interferencia de ARN , Resultado del Tratamiento
3.
Acta Psychiatr Scand ; 143(3): 189-205, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33315268

RESUMEN

OBJECTIVE: To systematically review evidence for the association between trauma experienced in childhood or adolescence, and the subsequent experience of affective or psychotic mental disorders in adulthood. METHODS: Electronic databases (Scopus, Medline (for Ovid), EMBASE and PsychINFO) were searched for peer-reviewed, longitudinal cohort studies in the English language examining child or adolescent exposure to trauma, and adult-diagnosed depression, anxiety, psychotic disorder or bipolar disorder. A total of 23 manuscripts were retained. RESULTS: Results revealed a significant association between the following childhood exposures and adult mental disorder: bullying (victimhood, perpetration and frequency); emotional abuse; physical neglect; parental loss; and general maltreatment (unspecified and/or multiple trauma exposure). There was some evidence of a dose-response relationship with those exposed to multiple forms of maltreatment having more than three times the odds of developing a mental disorder (Odds ratio = 3.11, 95% CI = 1.36-7.14). There was no significant association found between physical or sexual abuse and adult mental disorder; however, this is likely an artefact of how these adversities were assessed. CONCLUSION: There is strong evidence of an association between childhood trauma and later mental illness. This association is particularly evident for exposure to bullying, emotional abuse, maltreatment and parental loss. The evidence suggests that childhood and adolescence are an important time for risk for later mental illness, and an important period in which to focus intervention strategies.


Asunto(s)
Adultos Sobrevivientes del Maltrato a los Niños , Maltrato a los Niños , Trastornos Psicóticos , Adolescente , Adulto , Trastornos de Ansiedad , Niño , Estudios de Cohortes , Humanos , Estudios Longitudinales
4.
J Neurosci ; 39(26): 5064-5079, 2019 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-31015341

RESUMEN

Mesial temporal lobe epilepsy (mTLE) is a chronic neurological disease characterized by recurrent seizures. The antiepileptic drugs currently available to treat mTLE are ineffective in one-third of patients and lack disease-modifying effects. miRNAs, a class of small noncoding RNAs which control gene expression at the post-transcriptional level, play a key role in the pathogenesis of mTLE and other epilepsies. Although manipulation of miRNAs at acute stages has been reported to reduce subsequent spontaneous seizures, it is uncertain whether targeting miRNAs at chronic stages of mTLE can also reduce seizures. Furthermore, the functional role and downstream targets of most epilepsy-associated miRNAs remain poorly understood. Here, we show that miR-135a is selectively upregulated within neurons in epileptic brain and report that targeting miR-135a in vivo using antagomirs after onset of spontaneous recurrent seizures can reduce seizure activity at the chronic stage of experimental mTLE in male mice. Further, by using an unbiased approach combining immunoprecipitation and RNA sequencing, we identify several novel neuronal targets of miR-135a, including Mef2a Mef2 proteins are key regulators of excitatory synapse density. Mef2a and miR-135a show reciprocal expression regulation in human (of both sexes) and experimental TLE, and miR-135a regulates dendritic spine number and type through Mef2. Together, our data show that miR-135a is target for reducing seizure activity in chronic epilepsy, and that deregulation of miR-135a in epilepsy may alter Mef2a expression and thereby affect synaptic function and plasticity.SIGNIFICANCE STATEMENT miRNAs are post-transcriptional regulators of gene expression with roles in the pathogenesis of epilepsy. However, the precise mechanism of action and therapeutic potential of most epilepsy-associated miRNAs remain poorly understood. Our study reveals dramatic upregulation of the key neuronal miRNA miR-135a in both experimental and human mesial temporal lobe epilepsy. Silencing miR-135a in experimental temporal lobe epilepsy reduces seizure activity at the spontaneous recurrent seizure stage. These data support the exciting possibility that miRNAs can be targeted to combat seizures after spontaneous seizure activity has been established. Further, by using unbiased approaches novel neuronal targets of miR-135a, including members of the Mef2 protein family, are identified that begin to explain how deregulation of miR-135a may contribute to epilepsy.


Asunto(s)
Antagomirs/uso terapéutico , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Hipocampo/efectos de los fármacos , MicroARNs/antagonistas & inhibidores , Convulsiones/tratamiento farmacológico , Animales , Antagomirs/farmacología , Modelos Animales de Enfermedad , Epilepsia del Lóbulo Temporal/genética , Epilepsia del Lóbulo Temporal/metabolismo , Hipocampo/metabolismo , Factores de Transcripción MEF2/genética , Factores de Transcripción MEF2/metabolismo , Masculino , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Convulsiones/genética , Convulsiones/metabolismo , Resultado del Tratamiento
5.
BMC Infect Dis ; 20(1): 379, 2020 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-32460777

RESUMEN

BACKGROUND: Intestinal parasitic infections (IPIs) and anaemia are major health problems. This study assessed the prevalence of intestinal parasitic infections, anaemia and associated factors among pre-school children in rural areas of the Tigray region, northern Ethiopia. METHODS: A community based cross-sectional study was conducted among 610 pre-school children in rural communities of Northern Ethiopia from June 2017 to August 2017. Stool specimens were examined for the presence of trophozoites, cysts, oocysts, and ova using direct, formal-ethyl acetate concentration, Kato-Katz, and Ziehl-Neelsen techniques. Haemoglobin was measured using a HemoCue spectrometer. RESULTS: Among the 610 participating pre-school children in the study, the prevalence of IPIs and anaemia were 58% (95% conference interval (CI): 54.1-61.9%) and 21.6% (95% CI: 18.5-25.1%), respectively. Single, double, and triple parasitic infections were seen in 249 (41, 95% CI: 37-45%), 83 (14, 95% CI: 11-17%), and 22 (3.6, 95% CI: 2.4-5.4%) children, respectively. Of the seven intestinal parasitic organisms recorded from the participants, Entamoeba histolytica/dispar was the most prevalent 220 (36.1%) followed by Giardia lamblia 128 (20.1%), and Hymenolepis nana 102 (16.7%). Mixed infections were common among G. lamblia, E. histolytica/dispar and Cryptosporidium spp. oocyst. Intestinal parasitic infection prevalence increased from 47% in children aged 6-11 months to 66% in those aged 48-59 months; the prevalence ratio (PR) associated with a one-year increase in age was 1.08 (95% CI: 1.02-1.14, p = 0.009). Age-adjusted prevalence was higher in children who had been dewormed (PR = 1.2; 95% CI: 1.00-1.4, p = 0.045), and lower in households having two or more children aged under five (PR = 0.76, 95% CI: 0.61-0.95, p = 0.015). Anaemia rose from 28% in children aged 6-11 months to 43% in those aged 12-23 months, then fell continuously with age, reaching 7% in those aged 48-59 months. Age adjusted, anaemia was more prevalent in households using proper disposal of solid waste (PR = 1.5, 95% CI: 0.1-2.10, p = 0.009) while eating raw meat (PR = 0.49, 95% CI: 0.45-0.54, p = 0.000), any maternal education (PR = 0.64 95% CI: 0.52-0.79, p = 0.000), and household water treatment (PR = 0.75, 95% CI: 0.56-1.0, p = 0.044) were associated with lower prevalence of anaemia. CONCLUSIONS: More than half of the children were infected with intestinal parasites, while anaemia prevalence was concentrated in the 12-23 month age group. This study has identified a number of potentially modifiable risk factors to address the significant prevalence of IPIs and anaemia in these children. Improvements in sanitation, clean water, hand hygiene, maternal education could address both short and long-term consequences of these conditions in this vulnerable population.


Asunto(s)
Anemia/epidemiología , Parasitosis Intestinales/epidemiología , Anemia/parasitología , Animales , Niño , Preescolar , Estudios Transversales , Cryptosporidium/genética , Cryptosporidium/aislamiento & purificación , Entamoeba histolytica/genética , Entamoeba histolytica/aislamiento & purificación , Etiopía/epidemiología , Heces/parasitología , Femenino , Giardia lamblia/genética , Giardia lamblia/aislamiento & purificación , Higiene de las Manos , Humanos , Hymenolepis nana/genética , Hymenolepis nana/aislamiento & purificación , Lactante , Parasitosis Intestinales/parasitología , Intestinos/parasitología , Masculino , Prevalencia , Factores de Riesgo , Población Rural/estadística & datos numéricos , Saneamiento
6.
Platelets ; 31(4): 530-535, 2020 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-31530207

RESUMEN

Aspirin non-response is associated with poor outcome but there is no agreement between the different methods to asses it. Weight has been shown to be a predictor of poor response but only using one method. In this study, we determine the effects of weight on different assays of platelet function. The response to aspirin was determined in 138 cardiology patients using serum thromboxane, arachidonic acid-induced platelet aggregation and VerifyNow©. Twenty-five percent of patients showed an inadequate response to aspirin in at least one assay on the initial test. After ensuring patient compliance only 5% of patients were considered to be non-responders. Only 9% of non-responders were non-responsive in all three assays. When switched to plain aspirin, only 2% of patients were non-responsive. All patients responded adequately to 150 mg aspirin. The non-responders were significantly heavier than responders (78.5 kg ± 14.0 (SD); BMI: 28.4 kg/m2± 4.4 v's 102.6 kg ± 20.6, P = .0016; BMI: 38.3 kg/m2 ± 7.6, P= .0015). A rule-based approach of using plain aspirin in patients over 90 kg or BMI 32 along with patient education to ensure compliance will ensure that all patients respond to their aspirin without the need for testing.


Asunto(s)
Aspirina/farmacología , Plaquetas/efectos de los fármacos , Índice de Masa Corporal , Enfermedades Cardiovasculares/sangre , Agregación Plaquetaria/efectos de los fármacos , Tromboxano A2/sangre , Ácido Araquidónico/farmacología , Aspirina/análogos & derivados , Enfermedades Cardiovasculares/tratamiento farmacológico , Femenino , Humanos , Masculino , Inhibidores de Agregación Plaquetaria/farmacología , Pruebas de Función Plaquetaria , Tromboxano A2/uso terapéutico
7.
J Neurosci ; 36(22): 5920-32, 2016 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-27251615

RESUMEN

UNLABELLED: Neuroinflammation is thought to contribute to the pathogenesis and maintenance of temporal lobe epilepsy, but the underlying cell and molecular mechanisms are not fully understood. The P2X7 receptor is an ionotropic receptor predominantly expressed on the surface of microglia, although neuronal expression has also been reported. The receptor is activated by the release of ATP from intracellular sources that occurs during neurodegeneration, leading to microglial activation and inflammasome-mediated interleukin 1ß release that contributes to neuroinflammation. Using a reporter mouse in which green fluorescent protein is induced in response to the transcription of P2rx7, we show that expression of the receptor is selectively increased in CA1 pyramidal and dentate granule neurons, as well as in microglia in mice that developed epilepsy after intra-amygdala kainic acid-induced status epilepticus. P2X7 receptor levels were increased in hippocampal subfields in the mice and in resected hippocampus from patients with pharmacoresistant temporal lobe epilepsy. Cells transcribing P2rx7 in hippocampal slices from epileptic mice displayed enhanced agonist-evoked P2X7 receptor currents, and synaptosomes from these animals showed increased P2X7 receptor levels and altered calcium responses. A 5 d treatment of epileptic mice with systemic injections of the centrally available, potent, and specific P2X7 receptor antagonist JNJ-47965567 (30 mg/kg) significantly reduced spontaneous seizures during continuous video-EEG monitoring that persisted beyond the time of drug presence in the brain. Hippocampal sections from JNJ-47965567-treated animals obtained >5 d after treatment ceased displayed strongly reduced microgliosis and astrogliosis. The present study suggests that targeting the P2X7 receptor has anticonvulsant and possibly disease-modifying effects in experimental epilepsy. SIGNIFICANCE STATEMENT: Temporal lobe epilepsy is the most common and drug-resistant form of epilepsy in adults. Neuroinflammation is implicated as a pathomechanism, but the upstream mechanisms driving gliosis and how important this is for seizures remain unclear. In our study, we show that the ATP-gated P2X7 receptor is upregulated in experimental epilepsy and resected hippocampus from epilepsy patients. Targeting the receptor with a new centrally available antagonist, JNJ-47965567, suppressed epileptic seizures well beyond the time of treatment and reduced underlying gliosis in the hippocampus. The findings suggest a potential disease-modifying treatment for epilepsy based on targeting the P2X7 receptor.


Asunto(s)
Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Gliosis/tratamiento farmacológico , Gliosis/etiología , Antagonistas del Receptor Purinérgico P2X/uso terapéutico , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Adenosina Trifosfato/análogos & derivados , Adenosina Trifosfato/farmacología , Adolescente , Adulto , Animales , Encéfalo/metabolismo , Encéfalo/ultraestructura , Proteínas de Unión al Calcio/metabolismo , Modelos Animales de Enfermedad , Epilepsia del Lóbulo Temporal/patología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas de Microfilamentos/metabolismo , Persona de Mediana Edad , Proteínas del Tejido Nervioso/metabolismo , Niacinamida/análogos & derivados , Niacinamida/metabolismo , Niacinamida/farmacología , Niacinamida/uso terapéutico , Piperazinas/metabolismo , Piperazinas/farmacología , Piperazinas/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacología , Antagonistas del Receptor Purinérgico P2X/farmacología , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiología , Adulto Joven
8.
Epilepsy Behav ; 64(Pt A): 186-194, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27744244

RESUMEN

Animal models of status epilepticus are important tools to understand the pathogenesis of epileptic brain injury and evaluate potential seizure-suppressive, neuroprotective, and antiepileptogenic treatments. Focal elicitation of status epilepticus by intraamygdala kainic acid in mice produces unilateral hippocampal damage and the emergence of spontaneous recurrent seizures after a short latent period. The model has been characterized in C57BL/6, BALB/c, and SJL mice where strain-specific differences were found in the extent of hippocampal damage. 129/P mice are a common background strain for genetic models and may display unique characteristics in this model. We therefore compared responses to intraamygdala kainic acid between 129/P and C57BL/6 mice. Racine scale-scored convulsive behavior during status epilepticus was substantially lower in 129/P mice compared with that in C57BL/6 mice. Analysis of surface-recorded electroencephalogram (EEG) showed differences between strains in several frequency bands; EEG total power was greater during ictal episodes while duration of seizures was slightly shorter in 129/P mice. Histological analysis revealed similar hippocampal injury between strains, with neuronal death mainly confined to the ipsilateral CA3 subfield. Expression of genes associated with gliosis and neuroinflammatory responses was also similar between strains after seizures. Video-EEG telemetry recordings showed that 129/P mice first display spontaneous seizures within a few days of status epilepticus similar to C57BL/6 mice. However, high mortality in 129/P mice prevented a quantitative comparison of the epileptic seizure phenotypes between strains. This study defined behavioral, EEG, and histopathologic features of this mouse strain in a model increasingly useful for the study of the genetic contribution to acquired epilepsy. Intraamygdala kainic acid in 129/P mice could serve as a model of nonconvulsive status epilepticus, but long-term assessments will require model adjustment to mitigate the severity of the emergent epileptic phenotype.


Asunto(s)
Amígdala del Cerebelo/efectos de los fármacos , Modelos Animales de Enfermedad , Agonistas de Aminoácidos Excitadores/farmacología , Hipocampo , Ácido Kaínico/farmacología , Estado Epiléptico/inducido químicamente , Estado Epiléptico/fisiopatología , Animales , Conducta Animal , Electroencefalografía , Agonistas de Aminoácidos Excitadores/administración & dosificación , Hipocampo/metabolismo , Hipocampo/patología , Ácido Kaínico/administración & dosificación , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL
9.
Qual Life Res ; 22(9): 2549-59, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23504522

RESUMEN

PURPOSE: This study aims to evaluate the validity of current measurement models for the control, autonomy, self-realisation, and pleasure (CASP) measure of quality of life (QoL)-a second-order four-factor CASP-19 model and a second-order three-factor CASP-12 version-in a recent population survey. A previous large sample study did not report good fit for these measurement models. The study also aims to re-develop the model and propose a well-fitting alternative. METHODS: To evaluate the current measurement models, confirmatory factor analysis (CFA) was used. A cross-sectional sample (n = 6,823) representative of the Irish community-dwelling population aged 50 and over was obtained from the Irish Longitudinal Study of Ageing (TILDA). Model revision was based on descriptive statistics, exploratory factor analysis and examination of fit diagnostic statistics. Revised models were tested using CFA. RESULTS: The results of the CFA did not support the validity of the established measurement models. A reformulated 12-item, two-factor model comprising control/autonomy and self-realisation/pleasure, with residual covariances for negatively worded items, had excellent fit to the data (χ(2) 161.90, df = 44, p < 0.001; RMSEA = 0.03, 90 % CI 0.02-0.03), and a clearer conceptual rationale. The same model with one overall QoL factor had similar excellent fit. CONCLUSIONS: We recommend the use of the single-factor model (CASP-R12) when assessing overall quality of life. The dimensions of control/autonomy and self-realisation/pleasure can be examined separately by researchers interested in those constructs. Researchers using structural equation modelling can use the well-fitting measurement model outlined here including adjustment for residual covariances.


Asunto(s)
Autonomía Personal , Psicometría/instrumentación , Calidad de Vida , Autoimagen , Anciano , Envejecimiento/psicología , Análisis Factorial , Femenino , Humanos , Irlanda , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Características de la Residencia , Encuestas y Cuestionarios
10.
Psychol Assess ; 35(2): 95-114, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36689386

RESUMEN

The seven-item Hospital Anxiety and Depression Scale Depression subscale (HADS-D) and the total score of the 14-item HADS (HADS-T) are both used for major depression screening. Compared to the HADS-D, the HADS-T includes anxiety items and requires more time to complete. We compared the screening accuracy of the HADS-D and HADS-T for major depression detection. We conducted an individual participant data meta-analysis and fit bivariate random effects models to assess diagnostic accuracy among participants with both HADS-D and HADS-T scores. We identified optimal cutoffs, estimated sensitivity and specificity with 95% confidence intervals, and compared screening accuracy across paired cutoffs via two-stage and individual-level models. We used a 0.05 equivalence margin to assess equivalency in sensitivity and specificity. 20,700 participants (2,285 major depression cases) from 98 studies were included. Cutoffs of ≥7 for the HADS-D (sensitivity 0.79 [0.75, 0.83], specificity 0.78 [0.75, 0.80]) and ≥15 for the HADS-T (sensitivity 0.79 [0.76, 0.82], specificity 0.81 [0.78, 0.83]) minimized the distance to the top-left corner of the receiver operating characteristic curve. Across all sets of paired cutoffs evaluated, differences of sensitivity between HADS-T and HADS-D ranged from -0.05 to 0.01 (0.00 at paired optimal cutoffs), and differences of specificity were within 0.03 for all cutoffs (0.02-0.03). The pattern was similar among outpatients, although the HADS-T was slightly (not nonequivalently) more specific among inpatients. The accuracy of HADS-T was equivalent to the HADS-D for detecting major depression. In most settings, the shorter HADS-D would be preferred. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Asunto(s)
Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico , Depresión/diagnóstico , Escalas de Valoración Psiquiátrica , Sensibilidad y Especificidad , Ansiedad/diagnóstico , Tamizaje Masivo
11.
Mol Ther Nucleic Acids ; 28: 514-529, 2022 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-35592499

RESUMEN

Angelman syndrome (AS) is a severe neurodevelopmental disorder featuring ataxia, cognitive impairment, and drug-resistant epilepsy. AS is caused by mutations or deletion of the maternal copy of the paternally imprinted UBE3A gene, with current precision therapy approaches focusing on re-expression of UBE3A. Certain phenotypes, however, are difficult to rescue beyond early development. Notably, a cluster of microRNA binding sites was reported in the untranslated Ube3a1 transcript, including for miR-134, suggesting that AS may be associated with microRNA dysregulation. Here, we report levels of miR-134 and key targets are normal in the hippocampus of mice carrying a maternal deletion of Ube3a (Ube3a m-/p+ ). Nevertheless, intracerebroventricular injection of an antimiR oligonucleotide inhibitor of miR-134 (Ant-134) reduced audiogenic seizure severity over multiple trials in 21- and 42-day-old AS mice. Interestingly, Ant-134 also improved distance traveled and center crossings of AS mice in the open-field test. Finally, we show that silencing miR-134 can upregulate targets of miR-134 in neurons differentiated from Angelman patient-derived induced pluripotent stem cells. These findings indicate that silencing miR-134 and possibly other microRNAs could be useful to treat clinically relevant phenotypes with a later developmental window in AS.

12.
Cerebrovasc Dis ; 32(4): 385-92, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21986027

RESUMEN

BACKGROUND: Many countries are developing national audits of stroke care. However, these typically focus on stroke care from acute event to hospital discharge rather than the full spectrum from prevention to long-term care. We report on a comprehensive national audit of stroke care in the community and hospitals in the Republic of Ireland. The findings provide insights into the wider needs of people with stroke and their families, a basis for developing stroke-appropriate health strategies, and a global model for the evaluation of stroke services. METHODS: Six national surveys were completed: general practitioners (prevention and primary care), hospital organisational and clinical audit of 2,570 consecutive stroke admissions (acute and hospital care), allied health professionals and public health nurses (discharge to community care), nursing homes (needs of patients discharged to long-term care), and patient and carers (post-hospital phase of rehabilitation and ongoing care). RESULTS: The audit identified substantial deficits in a number of areas including primary prevention, emergency assessment/investigation and treatment in hospital, discharge planning, rehabilitation and ongoing secondary prevention, and communication with patients and families. There was a lack of coordination and communication between the acute and community services, with a dearth of therapy services in both home and nursing home settings. CONCLUSION: This multi-faceted national stroke audit facilitated multiple perspectives on the continuum of stroke prevention and care. An overall synthesis of surveys supports the development of a multidisciplinary perspective in planning the development of comprehensive stroke services at the national level, and may assist in regional and global development of stroke strategies.


Asunto(s)
Continuidad de la Atención al Paciente/normas , Auditoría Médica , Casas de Salud , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular/prevención & control , Recolección de Datos , Hospitalización , Humanos , Irlanda , Alta del Paciente/normas , Atención Primaria de Salud/normas , Prevención Secundaria/normas , Accidente Cerebrovascular/terapia , Resultado del Tratamiento
13.
Environ Sci Technol ; 45(18): 7862-7, 2011 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-21827166

RESUMEN

Recent solar disinfection (SODIS) studies in Bolivia and South Africa have reported compliance rates below 35% resulting in no overall statistically significant benefit associated with disease rates. In this study, we report the results of a 1 year randomized controlled trial investigating the effect of SODIS of drinking water on the incidence of dysentery and nondysentery diarrhea among children of age 6 months to 5 years living in rural communities in Cambodia. We compared 426 children in 375 households using SODIS with 502 children in 407 households with no intervention. Study compliance was greater than 90% with only 5% of children having less than 10 months of follow-up and 2.3% having less than 6 months. Adjusted for water source type, children in the SODIS group had a reduced incidence of dysentery, with an incidence rate ratio (IRR) of 0.50 (95% CI 0.27-0.93, p = 0.029). SODIS also had a protective effect against nondysentery diarrhea, with an IRR of 0.37 (95% CI 0.29-0.48, p < 0.001). This study suggests strongly that SODIS is an effective and culturally acceptable point-of-use water treatment method in the culture of rural Cambodia and may be of benefit among similar communities in neighboring South East Asian countries.


Asunto(s)
Diarrea/epidemiología , Desinfección/métodos , Agua Potable/microbiología , Disentería/epidemiología , Luz Solar , Purificación del Agua/métodos , Cambodia/epidemiología , Preescolar , Recuento de Colonia Microbiana , Conducta Cooperativa , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Población Rural
14.
Environ Sci Technol ; 45(21): 9315-23, 2011 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-21936492

RESUMEN

We report the results of a randomized controlled intervention study (September 2007 to March 2009) investigating the effect of solar disinfection (SODIS) of drinking water on the incidence of dysentery, nondysentery diarrhea, and anthropometric measurements of height and weight among children of age 6 months to 5 years living in peri-urban and rural communities in Nakuru, Kenya. We compared 555 children in 404 households using SODIS with 534 children in 361 households with no intervention. Dysentery was recorded using a pictorial diary. Incidence rate ratios (IRR) for both number of days and episodes of dysentery and nondysentery diarrhea were significantly (P < 0.001) reduced by use of solar disinfection: dysentery days IRR = 0.56 (95% CI 0.40 to 0.79); dysentery episodes IRR = 0.55 (95% CI 0.42 to 0.73); nondysentery days IRR = 0.70 (95% CI 0.59 to 0.84); nondysentery episodes IRR = 0.73 (95% CI 0.63 to 0.84). Anthropometry measurements of weight and height showed median height-for-age was significantly increased in those on SODIS, corresponding to an average of 0.8 cm over a 1-year period over the group as a whole (95% CI 0.7 to 1.6 cm, P = 0.031). Median weight-for-age was higher in those on SODIS, corresponding to a 0.23 kg difference in weight over the same period; however, the confidence interval spanned zero and the effect fell short of statistical significance (95% CI -0.02 to 0.47 kg, P = 0.068). SODIS and control households did not differ in the microbial quality of their untreated household water over the follow-up period (P = 0.119), but E. coli concentrations in SODIS bottles were significantly lower than those in storage containers over all follow-up visits (P < 0.001). This is the first trial to show evidence of the effect of SODIS on childhood anthropometry, compared with children in the control group and should alleviate concerns expressed by some commentators that the lower rates of dysentery associated with SODIS are the product of biased reporting rather than reflective of genuinely decreased incidence.


Asunto(s)
Desinfección/métodos , Disentería/prevención & control , Luz Solar , Purificación del Agua/métodos , Preescolar , Humanos , Lactante , Kenia
15.
J Public Health (Oxf) ; 33(4): 571-8, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21486871

RESUMEN

BACKGROUND: This study measured the acceptability of urine-based chlamydia screening to young adults, where young adults wanted opportunistic chlamydia screening services to be located, and by whom they wanted to be offered screening. METHODS: A cross-sectional survey of 5685 university students and 400 young adult healthcares setting attendees (age: 18-29 years). RESULTS: Ninety-six percent of males and 93% of females said that they would find it acceptable to be offered chlamydia screening. Seventy-six percent of males and 77% of females wanted to be offered screening by a doctor or nurse. Young women would prefer female staff. Most respondents preferred that screening be located in traditional healthcare settings such as General Practices, and offered by either doctors or nurses. More than 90% of respondents did not want screening services to be located in pharmacies and almost all rejected public non-health care screening settings. CONCLUSIONS: Opportunistic chlamydia screening services should be located in traditional healthcare/medical settings, and screening should be offered by doctors and nurses.


Asunto(s)
Infecciones por Chlamydia/diagnóstico , Chlamydia trachomatis/patogenicidad , Tamizaje Masivo/organización & administración , Aceptación de la Atención de Salud , Prioridad del Paciente/estadística & datos numéricos , Adolescente , Adulto , Centros Comunitarios de Salud , Estudios Transversales , Femenino , Médicos Generales , Humanos , Irlanda , Masculino , Tamizaje Masivo/estadística & datos numéricos , Enfermeras Practicantes , Estudiantes , Encuestas y Cuestionarios , Adulto Joven
16.
Eur J Public Health ; 21(1): 98-103, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20639191

RESUMEN

BACKGROUND: Sexual violence is a worldwide problem affecting children and adults. Knowledge of trends in prevalence is essential to inform the design and evaluation of preventive and intervention programmes. We aimed to assess the prevalence of lifetime sexual violence for both sexes and to document the prevalence of adult and child abuse by birth year in the general population. METHODS: National cluster-randomized telephone interview study of 3120 adults in Ireland was done. RESULTS: Child sexual abuse involving physical contact was reported by 20% of women and 16% of men. In adulthood, figures were 20% and 10% for women and men, respectively. Prevalence of any form of sexual violence across the lifespan was 42% (women) and 38% (men). Analysis by year of birth indicated a curvilinear pattern for child sexual abuse with lower prevalence in the oldest and youngest participants. Sexual violence in young adulthood showed a linear pattern with higher prevalence in the youngest participants. CONCLUSION: The trend of lower rates of experience of child sexual abuse in younger adults in the sample is in keeping with findings from other countries. The trend of higher rates of adult sexual violence in younger adults is worrying, particularly since the same participants reported less experience of child sexual abuse than the preceding generations. There is a paucity of international data addressing the issue of cohort differences in exposure to sexual violence. Within-study analysis, and follow-up studies designed to maximize replicability, are needed to inform discussion about societal trends in different types of sexual violence.


Asunto(s)
Delitos Sexuales/estadística & datos numéricos , Delitos Sexuales/tendencias , Adolescente , Adulto , Factores de Edad , Anciano , Abuso Sexual Infantil/estadística & datos numéricos , Abuso Sexual Infantil/tendencias , Estudios de Cohortes , Femenino , Humanos , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Factores Sexuales , Adulto Joven
17.
Aging Ment Health ; 15(8): 985-94, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21749221

RESUMEN

OBJECTIVES: In this study, we examine the prevalence and distribution of worry, its content, and its associations with quality of life and depression, based on a large sample of community-dwelling elderly. We will attempt to distinguish between pathological and non-pathological worry based on these associations. DESIGN: Community survey. SETTING: Inner-city population. PARTICIPANTS: A total of 2136 people aged between 65 and 96, of whom 66% were women, were recruited through general practitioners and interviewed in their own homes. MEASUREMENTS: The GMS-AGECAT structured psychiatric interview was used to rate symptoms which were classified into five levels of severity of worry ranging from simple, non-excessive to generalised anxiety disorder (GAD). RESULTS: In this study, 79% of the participants reported worrying, 37% worrying excessively, while 20% reported excessive, uncontrollable worry and 6.3% met criteria for GAD. Prevalence of all types of worry declined with age and was lower in men. The prevalence of depressed mood was similar in those without worry and those with non-severe worry (Wald post hoc test, p = 0.06) but rose significantly with each level of severe worry (Wald post hoc tests, all p < 0.05). Major depressive disorder was absent in those who did not worry, and had a prevalence of only 0.2% in those with non-severe worry (p = 0.552, Fisher's exact test). It has a significantly elevated prevalence at all levels of excessive worry, and a significantly higher prevalence in those with GAD. All levels of excessive worry were associated with reduced quality of life. CONCLUSION: Severe worry is highly prevalent in the elderly; most severe worriers do not meet criteria for GAD, but have a reduced quality of life and an increased prevalence of depression.


Asunto(s)
Ansiedad/epidemiología , Anciano , Anciano de 80 o más Años , Ansiedad/fisiopatología , Trastorno Depresivo Mayor/epidemiología , Femenino , Encuestas Epidemiológicas , Humanos , Entrevista Psicológica , Irlanda/epidemiología , Masculino , Satisfacción Personal , Calidad de Vida/psicología , Índice de Severidad de la Enfermedad
18.
J Clin Nurs ; 20(17-18): 2633-44, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21702861

RESUMEN

UNLABELLED: BACKGROUNDL: Pressure ulcers are common, costly and impact negatively on individuals. Pressure is the prime cause, and immobility is the factor that exposes individuals to pressure. International guidelines advocate repositioning; however, there is confusion surrounding the best method and frequency required. DESIGN: A pragmatic, multi-centre, open label, prospective, cluster-randomised controlled trial was conducted to compare the incidence of pressure ulcers among older persons nursed using two different repositioning regimens. METHOD: Ethical approval was received. Study sites (n=12) were allocated to study arm using cluster randomisation. The experimental group (n=99) were repositioned three hourly at night, using the 30° tilt; the control group (n=114) received routine prevention (six-hourly repositioning, using 90° lateral rotation). Data analysis was by intention to treat; follow-up was for four weeks. RESULTS: All participants (n=213) were Irish and white, among them 77% were women and 65% aged 80 years or older. Three patients (3%) in the experimental group and 13 patients (11%) in the control group developed a pressure ulcer (p=0·035; 95% CI 0·031-0·038; ICC=0·001). All pressure ulcers were grade 1 (44%) or grade 2 (56%). Mobility and activity were the highest predictors of pressure ulcer development (ß=-0·246, 95% CI=-0·319 to -0·066; p=0·003); (ß=0·227, 95% CI=0·041-0·246; p = 0·006). CONCLUSION: Repositioning older persons at risk of pressure ulcers every three hours at night, using the 30° tilt, reduces the incidence of pressure ulcers compared with usual care. The study supports the recommendations of the 2009 international pressure ulcer prevention guidelines. RELEVANCE TO CLINICAL PRACTICE: An effective method of pressure ulcer prevention has been identified; in the light of the problem of pressures ulcers, current prevention strategies should be reviewed. It is important to implement appropriate prevention strategies, of which repositioning is one.


Asunto(s)
Postura , Úlcera por Presión/prevención & control , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino
19.
BMJ Qual Saf ; 30(7): 547-558, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33436402

RESUMEN

OBJECTIVES: To quantify the prevalence and nature of adverse events in acute Irish hospitals in 2015 and to assess the impact of the National Clinical Programmes and the National Clinical Guidelines on the prevalence of adverse events by comparing these results with the previously published data from 2009. DESIGN AND METHODS: A retrospective chart review of 1605 admissions to eight Irish hospitals in 2015, using identical methods to those used in 2009. RESULTS: The percentage of admissions associated with one or more adverse events was unchanged (p=0.48) at 14% (95% CI=10.4% to 18.4%) in 2015 compared with 12.2% (95% CI=9.5% to 15.5%) in 2009. Similarly, the prevalence of preventable adverse events was unchanged (p=0.3) at 7.4% (95% CI=5.3% to 10.5%) in 2015 compared with 9.1% (95% CI=6.9% to 11.9%) in 2009. The incidence densities of preventable adverse events were 5.6 adverse events per 100 admissions (95% CI=3.4 to 8.0) in 2015 and 7.7 adverse events per 100 admissions (95% CI=5.8 to 9.6) in 2009 (p=0.23). However, the percentage of preventable adverse events due to hospital-associated infections decreased to 22.2% (95% CI=15.2% to 31.1%) in 2015 from 33.1% (95% CI=25.6% to 41.6%) in 2009 (p=0.01). CONCLUSION: Adverse event rates remained stable between 2009 and 2015. The percentage of preventable adverse events related to hospital-associated infection decreased, which may represent a positive impact of the related national programmes and guidelines.


Asunto(s)
Hospitalización , Hospitales , Atención a la Salud , Humanos , Incidencia , Estudios Retrospectivos
20.
Sci Rep ; 11(1): 9927, 2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33976287

RESUMEN

Convalescent plasma (CP) therapy in COVID-19 disease may improve clinical outcome in severe disease. This pilot study was undertaken to inform feasibility and safety of further definitive studies. This was a prospective, interventional and randomized open label pilot trial in patients with severe COVID-19. Twenty COVID-19 patients received two 200 ml transfusions of convalescent patient CP over 24-h compared with 20 who received standard of care. The primary outcome was the requirement for ventilation (non-invasive or mechanical ventilation). The secondary outcomes were biochemical parameters and mortality at 28 days. The CP group were a higher risk group with higher ferritin levels (p < 0.05) though respiratory indices did not differ. The primary outcome measure was required in 6 controls and 4 patients on CP (risk ratio 0.67, 95% CI 0.22-2.0, p = 0.72); mean time on ventilation (NIV or MV) did not differ. There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm. There were no significant differences in the primary or secondary outcome measures between CP and standard therapy, although a larger definitive study is needed for confirmation. However, the study did show that CP therapy appears to be safe in hospitalized COVID-19 patients with hypoxia.Clinical trials registration NCT04356534: 22/04/2020.


Asunto(s)
COVID-19/terapia , Adulto , Anciano , COVID-19/mortalidad , COVID-19/patología , COVID-19/virología , Femenino , Ferritinas/metabolismo , Humanos , Inmunización Pasiva , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Respiración Artificial/estadística & datos numéricos , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del Tratamiento , Sueroterapia para COVID-19
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