Modafinil Reverses Phencyclidine-Induced Deficits in Cognitive Flexibility,Cerebral Metabolism,and Functional Brain Connectivity

Objective:

In the present study, we employ mathematical modeling (partial least squares regression, PLSR) to elucidate the functional connectivity signatures of discrete brain regions in order to identify the functional networks subserving PCP-induced disruption of distinct cognitive functions and their restoration by the procognitive drug modafinil.

Methods:

We examine the functional connectivity signatures of discrete brain regions that show overt alterations in metabolism, as measured by semiquantitative 2-deoxyglucose autoradiography, in an animal model (subchronic phencyclidine [PCP] treatment), which shows cognitive inflexibility with relevance to the cognitive deficits seen in schizophrenia.

Results:

We identify the specific components of functional connectivity that contribute to the rescue of this cognitive inflexibility and to the restoration of overt cerebral metabolism by modafinil. We demonstrate that modafinil reversed both the PCP-induced deficit in the ability to switch attentional set and the PCP-induced hypometabolism in the prefrontal (anterior prelimbic) and retrosplenial cortices. Furthermore, modafinil selectively enhanced metabolism in the medial prelimbic cortex. The functional connectivity signatures of these regions identified a unifying functional subsystem underlying the influence of modafinil on cerebral metabolism and cognitive flexibility that included the nucleus accumbens core and locus coeruleus. In addition, these functional connectivity signatures identified coupling events specific to each brain region, which relate to known anatomical connectivity.

Conclusions:

These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction.     

Challenges to Remaining at Work with Common Health Problems: What Helps and What Influence Do Organisational Policies Have?

Introduction: Common health problems have a significant impact on work productivity (presenteeism), and sickness absence. The aim of this study was to examine the attitudes and beliefs of employees in the public sector about common health problems and work using the Flags system as a conceptual framework to identify problems and potential solutions. Method: 63 employees took part in 14 focus groups in two public sector organisations. Discussions were audio-recorded, transcribed, and analysed thematically using NVivo. Results: The study confirmed the importance of heath-focused clinical factors (Yellow flags), perceptions of work (Blue flags), and more objective characteristics of work and organisational policies (Black flags), which emerged as major themes. The social and moral norms surrounding sickness absence and presenteeism were frequently discussed, including the impact of absence on colleagues, guilt, legitimising illness, and trust. There were interactions between the different Flags, often mediated by managers via their relationships with employees and their role in implementing organisational policy. Conclusions: The Flags system was useful as a conceptual framework in this context for identifying a number of obstacles to working with health problems, many of which were potentially modifiable on worker, workplace, or wider systems levels.     

Management of sacrococcygeal pilonidal sinus disease

The ideal treatment for patients who suffer from pilonidal sinus disease should lead to a cure with a rapid recovery period allowing a return to normal daily activities, with a low level of associated morbidity. A variety of different surgical techniques have been described for the primary treatment of pilonidal sinus disease and current practice remains variable and contentious. Whilst some management options have improved outcomes for some patients, the complications of surgery, particularly related to wound healing, often remain worse than the primary disease. This clinical review aims to provide an update on the management options to guide clinicians involved in the care of patients who suffer from sacrococcygeal pilonidal sinus disease.