RESUMO
Current pharmacological treatments for bipolar disorder are inadequate and based on serendipitously discovered drugs often with limited efficacy, burdensome side-effects, and unclear mechanisms of action. Advances in drug development for the treatment of bipolar disorder remain incremental and have come largely from repurposing drugs used for other psychiatric conditions, a strategy that has failed to find truly revolutionary therapies, as it does not target the mood instability that characterises the condition. The lack of therapeutic innovation in the bipolar disorder field is largely due to a poor understanding of the underlying disease mechanisms and the consequent absence of validated drug targets. A compelling new treatment target is the Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) enzyme. CaMKK2 is highly enriched in brain neurons and regulates energy metabolism and neuronal processes that underpin higher order functions such as long-term memory, mood, and other affective functions. Loss-of-function polymorphisms and a rare missense mutation in human CAMKK2 are associated with bipolar disorder, and genetic deletion of Camkk2 in mice causes bipolar-like behaviours similar to those in patients. Furthermore, these behaviours are ameliorated by lithium, which increases CaMKK2 activity. In this review, we discuss multiple convergent lines of evidence that support targeting of CaMKK2 as a new treatment strategy for bipolar disorder.
Assuntos
Transtorno Bipolar , Animais , Humanos , Camundongos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/genética , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/genética , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Mutação de Sentido IncorretoRESUMO
Intubating laryngeal mask airways can be used to provide continuous ventilation throughout intubation. This is a case of a morbidly obese (body mass index = 58) 65-year-old woman with T10 and T11 compression fractures. Optimal positioning for airway management was hindered by her unstable spine, minimal neck range of motion, and extreme pain with any movement. An intubating laryngeal mask airway was placed in the awake, topically anesthetized patient, and the laryngeal mask airway and endotracheal tube combination was left in place throughout surgery.
Assuntos
Fraturas por Compressão/complicações , Intubação Intratraqueal/métodos , Máscaras Laríngeas , Obesidade Mórbida/complicações , Fraturas da Coluna Vertebral/complicações , Espondilite Anquilosante/complicações , Vigília , Idoso , Feminino , Humanos , Intubação Intratraqueal/instrumentação , Dor/complicações , Amplitude de Movimento ArticularRESUMO
This research investigates vet and vet nurse career identity through the qualitative methodology of narrative enquiry. It derives learning and understanding from these empirical data to assist the veterinary profession to adjust to the changing industry landscape. Through a case series of 20 vets and vet nurses' career stories, this paper seeks understanding about career identity and its impact on individuals and organisations in the light of industry consolidation. Findings suggest that career is central to identity for many veterinary professionals who tend to have a strong sense of self; this is particularly evident around self as learner and technically competent, teacher and educator, ethical and moral and dedicated and resilient. Consequently, mismatches between 'who I am' and 'what I do' tend not to lead to identity customisation (to fit self into role or organisation) but to the search for alternative, more identity-compatible employment. This study offers a valuable insight for employers, veterinary professionals and universities. It suggests that businesses can gain competitive advantage and employees achieve validation and enrichment by working towards organisational and individual identity congruence and that teaching veterinary professionals with contemporary business in mind may develop graduates with a more sustainable identity.