From the Cover: Loss of phosphatidylinositol 4-kinase 2α activity causes late onset degeneration of spinal cord axons

Phosphoinositide (PI) lipids are intracellular membrane signaling intermediates and effectors produced by localized PI kinase and phosphatase activities. Although many signaling roles of PI kinases have been identified in cultured cell lines, transgenic animal studies have produced unexpected insight into the in vivo functions of specific PI 3- and 5-kinases, but no mammalian PI 4-kinase (PI4K) knockout has previously been reported. Prior studies using cultured cells implicated the PI4K2α isozyme in diverse functions, including receptor signaling, ion channel regulation, endosomal trafficking, and regulated secretion. We now show that despite these important functions, mice lacking PI4K2α kinase activity initially appear normal. However, adult Pi4k2a^GT/GT animals develop a progressive neurological disease characterized by tremor, limb weakness, urinary incontinence, and premature mortality. Histological analysis of aged Pi4k2a^GT/GT animals revealed lipofuscin-like deposition and gliosis in the cerebellum, and loss of Purkinje cells. Peripheral nerves are essentially normal, but massive axonal degeneration was found in the spinal cord in both ascending and descending tracts. These results reveal a previously undescribed role for aberrant PI signaling in neurological disease that resembles autosomal recessive hereditary spastic paraplegia.     

Regenerative peripheral nerve interfaces for real-time,proportional control of a Neuroprosthetic hand

Introduction

Regenerative peripheral nerve interfaces (RPNIs) are biological constructs which amplify neural signals and have shown long-term stability in rat models. Real-time control of a neuroprosthesis in rat models has not yet been demonstrated. The purpose of this study was to: a) design and validate a system for translating electromyography (EMG) signals from an RPNI in a rat model into real-time control of a neuroprosthetic hand, and; b) use the system to demonstrate RPNI proportional neuroprosthesis control.

Methods

Animals were randomly assigned to three experimental groups: (1) Control; (2) Denervated, and; (3) RPNI. In the RPNI group, the extensor digitorum longus (EDL) muscle was dissected free, denervated, transferred to the lateral thigh and neurotized with the residual end of the transected common peroneal nerve. Rats received tactile stimuli to the hind-limb via monofilaments, and electrodes were used to record EMG. Signals were filtered, rectified and integrated using a moving sample window. Processed EMG signals (iEMG) from RPNIs were validated against Control and Denervated group outputs.

Results

Voluntary reflexive rat movements produced signaling that activated the prosthesis in both the Control and RPNI groups, but produced no activation in the Denervated group. Signal-to-Noise ratio between hind-limb movement and resting iEMG was 3.55 for Controls and 3.81 for RPNIs. Both Control and RPNI groups exhibited a logarithmic iEMG increase with increased monofilament pressure, allowing graded prosthetic hand speed control (R²?=?0.758 and R²?=?0.802, respectively).

Conclusion

EMG signals were successfully acquired from RPNIs and translated into real-time neuroprosthetic control. Signal contamination from muscles adjacent to the RPNI was minimal. RPNI constructs provided reliable proportional prosthetic hand control.

     

Spillover Effects of the Affordable Care Act? Exploring the Impact on Young Adult Dental Insurance Coverage

ObjectivesTo assess whether the Affordable Care Act’s (ACA) dependent coverage health insurance mandate had a spillover impact on young adult dental insurance coverage and whether any observed effects varied by household income.DataMedical Expenditure Panel Surveys from 2006 through 2011.ResultsPrivate dental insurance increased by 6.7 percentage points among young adults compared to a control group of 27–30-year olds. Increases were concentrated at middle-income levels (125–400 percent FPL).ConclusionsThe dependent coverage mandate provision of the Affordable Care Act has not only increased health insurance rates among young adults but also dental insurance coverage rates.     

Disaster Training in 24 Hours: Evaluation of a Novel Medical Student Curriculum in Disaster Medicine

Background

Over a decade ago, the Association of American Medical Colleges called for incorporation of disaster medicine training into the education of medical students in the United States. Despite this recommendation, similar suggestions by other professional organizations, and significant interest from medical students and educators, few medical schools explicitly include robust disaster training in their curricula.

Doctors’ perspectives on the barriers to appropriate prescribing in older hospitalized patients: a qualitative study

Aims

Older patients commonly suffer from multimorbidites and take multiple medications. As a result, these patients are more vulnerable to potentially inappropriate prescribing (PIP). PIP in older patients may result in adverse drug events (ADEs) and hospitalizations. However, little has been done to identify why PIP occurs. The objectives of this study were (i) to identify hospital doctors'' perceptions as to why PIP occurs, (ii) to identify the barriers to addressing the issues identified and (iii) to determine which intervention types would be best suited to improving prescribing.

Methods

Semi-structured interviews based on the Theoretical Domains Framework (TDF), a tool used to apply behaviour change theories, were conducted with 22 hospital doctors. Content analysis was conducted to identify domains of the TDF that could be targeted to improve prescribing for older people. These domains were then mapped to the behaviour change wheel to identify possible intervention types.

Results

Content analysis identified five of the 12 domains in the TDF as relevant: (i) environmental context and resources, (ii) knowledge, (iii) skills, (iv) social influences and (v) memory/attention and decision processes. Using the behaviour change wheel, the types of interventions deemed suitable were those based on training and environmental restructuring.

Conclusion

This study shows that doctors feel there is insufficient emphasis on geriatric pharmacotherapy in their undergraduate/postgraduate training. An intervention providing supplementary training, with particular emphasis on decision processes and dealing with social influences would be justified. This study has, however, uncovered many areas for potential intervention in the future.     

Laser and brachytherapy in the palliation of adenocarcinoma of the oesophagus and cardia.

BACKGROUND: Palliation of malignant dysphagia is possible by a variety of methods although all have significant drawbacks. Laser therapy is an effective and safe treatment but has to be repeated at four to five weekly intervals to maintain palliation. A means of augmenting the benefits while reducing the need for repeat treatments would be highly beneficial to these patients. AIMS: To prospectively explore the safety and efficacy of intraluminal radiotherapy (brachytherapy) when used to augment laser recanalisation for malignant dysphagia. PATIENTS: Nineteen patients with dysphagia due to advanced adenocarcinoma of the oesophagus or cardia were recruited. METHODS: All patients received laser recanalisation until able to swallow a soft diet or better, before the application of a single dose of brachytherapy (10 Gy at 1 cm from the source). Patients were followed up and treated promptly by further endoscopic means in the event of their dysphagia worsening. RESULTS: Six patients (32%) required no further treatment until death at a median of 10 weeks (range 1-20 weeks). Further therapy was required at a median of 11 weeks (range 4-37 weeks) after brachytherapy for those 13 patients with recurrent dysphagia. Subsequent symptom control required endoscopic intervention at an average of once every nine weeks. There was no mortality associated with laser or brachytherapy. Median survival from initial treatment and including the one survivor was 36 weeks (range 5-132 weeks). CONCLUSIONS: Laser plus brachytherapy offers a safe and effective means of palliating malignant dysphagia due to adenocarcinoma, with a longer dysphagia free interval than historical controls treated with laser alone.