RESUMEN
Bovine mastitis is an inflammation of the mammary gland, and it is the most common infectious disease in dairy cattle. Mastitis reduces milk yield and quality, costing dairy farmers millions of dollars each year. The aim of this study was to develop a point-of-need test for identifying mastitis pathogens that is field portable, cost-effective and can be used with minimal training. Using a proprietary polymer-based milk sample preparation method to rapidly extract pathogen DNA in milk samples, we demonstrated quantitative Polymerase Chain Reaction (qPCR) assays for six common bovine bacterial mastitis pathogens: Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis, Mycoplasma bovis and Escherichia coli. We also implemented this sample preparation method on a prototype point-of-need system in a proof-of-concept field trial to evaluate user experience. Importantly, the protype system enabled a sample-to-result turnaround time of within 70 min to quantitatively detect all six target pathogens. The key advantage of our point-of-need prototype system is being culture-independent yet providing automated milk sample preparation for molecular identification of key mastitis pathogens by non-expert users. Our point-of-need prototype system showed a good correlation to laboratory-based qPCR for target pathogen detection outcomes, thus potentially removing the need for milk samples to be transported off-site for laboratory testing. Above all, we successfully achieved our objective of developing a point-of-need biosensor technology for mastitis and increased its readiness level with industry partners towards technology commercialization.
Asunto(s)
Técnicas Biosensibles , Mastitis Bovina , Leche , Animales , Leche/microbiología , Mastitis Bovina/diagnóstico , Mastitis Bovina/microbiología , Bovinos , Técnicas Biosensibles/métodos , Femenino , ADN Bacteriano/análisis , ADN Bacteriano/aislamiento & purificación , ADN Bacteriano/genética , Sistemas de Atención de Punto , Reacción en Cadena en Tiempo Real de la Polimerasa , Streptococcus/aislamiento & purificación , Streptococcus/genéticaRESUMEN
The recent approval of formulations of the endogenous neurosteroid allopregnanolone (brexanolone) and the synthetic neuroactive steroid SAGE-217 (zuranolone) to treat postpartum depression (PPD) has encouraged further research to elucidate why these potent enhancers of GABAAR function are clinically effective in this condition. Dopaminergic projections from the ventral tegmental area (VTA) to the nucleus accumbens are associated with reward/motivation and brain imaging studies report that individuals with PPD show reduced activity of this pathway in response to reward and infant engagement. However, the influence of neurosteroids on GABA-ergic transmission in the nucleus accumbens has received limited attention. Here, we investigate, in the medium spiny neurons (MSNs) of the mouse nucleus accumbens core, the effect of allopregnanolone, SAGE-217 and other endogenous and synthetic steroids of interest on fast phasic and tonic inhibition mediated by synaptic (α1/2ßγ2) and extrasynaptic (α4ßδ) GABAARs, respectively. We present evidence suggesting the resident tonic current results from the spontaneous opening of δ-GABAARs, where the steroid-enhanced tonic current is GABA-dependent. Furthermore, we demonstrate local neurosteroid synthesis in the accumbal slice preparation and reveal that GABA-ergic neurotransmission of MSNs is influenced by an endogenous neurosteroid tone. Given the dramatic fluctuations in allopregnanolone levels during pregnancy and postpartum, this neurosteroid-mediated local fine-tuning of GABAergic transmission in the MSNs will probably be perturbed.
Asunto(s)
Neuroesteroides , Núcleo Accumbens , Pregnanolona , Receptores de GABA-A , Animales , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efectos de los fármacos , Ratones , Receptores de GABA-A/metabolismo , Neuroesteroides/metabolismo , Pregnanolona/farmacología , Pregnanolona/metabolismo , Sinapsis/metabolismo , Sinapsis/efectos de los fármacos , Ratones Endogámicos C57BL , Femenino , Masculino , Transmisión Sináptica/efectos de los fármacos , Neuronas/metabolismo , Neuronas/efectos de los fármacosRESUMEN
Studies in the 1980s revealed endogenous metabolites of progesterone and deoxycorticosterone to be potent, efficacious, positive allosteric modulators (PAMs) of the GABAA receptor (GABAA R). The discovery that such steroids are locally synthesised in the central nervous system (CNS) promoted the thesis that neural inhibition in the CNS may be "fine-tuned" by these neurosteroids to influence behaviour. In preclinical studies, these neurosteroids exhibited anxiolytic, anticonvulsant, analgesic and sedative properties and, at relatively high doses, induced a state of general anaesthesia, a profile consistent with their interaction with GABAA Rs. However, realising the therapeutic potential of either endogenous neurosteroids or synthetic "neuroactive" steroids has proven challenging. Recent approval by the Food and Drug Administration of the use of allopregnanolone (brexanolone) to treat postpartum depression has rekindled enthusiasm for exploring their potential as new medicines. Although neurosteroids are selective for GABAA Rs, they exhibit little or no selectivity across the many GABAA R subtypes. Nevertheless, a relatively minor population of receptors incorporating the δ-subunit (δ-GABAA Rs) appears to be an important contributor to their behavioural effects. Here, we consider how neurosteroids acting upon GABAA Rs influence neuronal signalling, as well as how such effects may acutely and persistently influence behaviour, and explore the case for developing selective PAMs of δ-GABAA R subtypes for the treatment of psychiatric disorders.
Asunto(s)
Neuroesteroides , Sistema Nervioso Central/metabolismo , Femenino , Humanos , Receptores de GABA-A/metabolismo , Transmisión Sináptica/fisiología , Ácido gamma-Aminobutírico/fisiologíaRESUMEN
BACKGROUND: There is no clear treatment pathway for people presenting to Australian emergency departments with deliberate self-harm. PURPOSE: To explore variations in mental health nurses' disposition decisions for patients following risk assessment for deliberate self-harm. DESIGN AND METHOD: A survey was distributed to mental health nurses. This survey comprised demographic items and questions in response to nine vignettes describing episodes of deliberate self-harm. Dispositional decision and reasoning were also sought for each vignette. FINDINGS: Poor levels of agreement for disposition were found. PRACTICE IMPLICATIONS: There was a lack of consensus regarding dispositional outcomes. This suggests a high level of subjectivity in decision-making which needs to be taken into account within clinical governance.
Asunto(s)
Actitud del Personal de Salud , Toma de Decisiones Clínicas , Servicio de Urgencia en Hospital/organización & administración , Enfermería Psiquiátrica/normas , Conducta Autodestructiva/enfermería , Australia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rol de la Enfermera , Relaciones Enfermero-Paciente , Medición de Riesgo , Encuestas y CuestionariosRESUMEN
Adults described and dated two kinds of first remembrances: a personal event memory (the recollection of a personal episode that had occurred at some time in some place) and a memory fragment (an isolated memory moment having no event context and remembered, perhaps, as an image, a behavior, or an emotion). First fragment memories were judged to have originated substantially earlier in life than first event memories--approximately 3 1/3 years of age for first fragment memories versus roughly 4 years of age for first event memories. We conclude that the end of childhood amnesia is marked not by our earliest episodic memories, but by the earliest remembered fragments of childhood experiences.
Asunto(s)
Amnesia , Memoria , Adulto , Niño , Humanos , Juicio , Recuerdo MentalRESUMEN
False recognition of an extralist word that is thematically related to all words of a study list may reflect internal activation of the theme word during encoding followed by impaired source monitoring at retrieval, that is, difficulty in determining whether the word had actually been experienced or merely thought of. To assist source monitoring, distinctive visual or verbal contexts were added to study words at input. Both types of context produced similar effects: False alarms to theme-word (critical) lures were reduced; remember judgements of critical lures called old were lower; and if contextual information had been added to lists, subjects indicated as much for list items and associated critical foils identified as old. The visual and verbal contexts used in the present studies were held to disrupt semantic categorisation of list words at input and to facilitate source monitoring at output.
Asunto(s)
Cognición/fisiología , Memoria/fisiología , Reconocimiento en Psicología/fisiología , Análisis de Varianza , Discriminación en Psicología , Humanos , Juicio , Modelos Psicológicos , Pruebas Psicológicas , Lectura , Aprendizaje Verbal/fisiología , Percepción Visual/fisiología , VocabularioRESUMEN
When adults are asked to report and date personal memories of their pasts, they show childhood amnesia, that is, diminished recall of experiences over the childhood years. This way of demonstrating the phenomenon was supplemented in the present study with a more direct approach: Participants reported events of early childhood that they knew they had experienced (because of family stories, photographs, etc.) but did not actually remember. The resulting cumulative relative frequency distributions produced by the two methods were substantially different, with the median age of remembered events being 6.07 years and of known events, 3.20 years. We suggest that the mean of these two ages, 4.64 years, gives a good indication of when childhood amnesia is eclipsed by personal memories in adults' recall of their personal pasts.