Cell directional spread determines accuracy,precision, and length of the neuronal population vector

The neuronal population vector (NPV) for movement direction is the sum of weighted neuronal directional contributions. Based on theoretical considerations, we proposed recently that the sharpness of tuning will impact the directional precision, accuracy, and length of the NPV, such that sharper tuning will yield NPV with higher precision, higher accuracy, and shorter length (Mahan and Georgopoulos in Front Neural Circuits 7:92, 2013). Furthermore, we proposed that controlling the inhibitory drive in a local network could be the mechanism by which the sharpness of directional tuning would be varied, resulting in a continuous specification and control of movement’s directional precision, accuracy, and speed (Mahan and Georgopoulos in Front Neural Circuits 7:92, 2013, Fig. 5). As a first step in testing this idea, here we analyzed data from 899 cells recorded in the motor cortex during performance of a center → out task. There were two major findings. First, directional selectivity varied with cell activity, such that it was higher in cells with lower mean discharge rates. And second, NPVs calculated from subsets of cells with higher directional selectivity (and, correspondingly, lower mean discharge rates) were more accurate (i.e., closer to the movement), precise (i.e., less variable), and shorter (i.e., slower; Schwartz in Science 265:540–542, 1994). These findings confirm our predictions above made from modeling (Mahan and Georgopoulos in Front Neural Circuits 7:92, 2013) and provide a simple mechanism by which desired attributes of the directional motor command can be implemented. We hypothesize that the inhibitory drive in a local network is controlled directly and independently of recurrent collaterals or common excitatory inputs to other cells. This could be achieved by a private excitation/inhibition of key inhibitory interneurons in a way similar to that in operation for Renshaw cells in the spinal cord. The presence of such a private line of inhibitory control remains to be investigated.     

Long-term impact of multifactorial treatment on new-onset diabetes and related cardiovascular events in metabolic syndrome: a post hoc ATTEMPT analysis

This post hoc analysis of the Assessing The Treatment Effect in Metabolic Syndrome Without Perceptible diabeTes (ATTEMPT) study assesses the 3? year incidence of new-onset diabetes (NOD) and related cardiovascular disease (CVD) events in patients with metabolic syndrome (MetS), after multifactorial (lifestyle and drug, including atorvastatin) intervention. Patients were randomized to group A (low-density lipoprotein cholesterol [LDL-C] target < 100 mg/dL) and group B (< 130 mg/dL). The incidence of NOD during the 42-month follow-up was very low, 0.83 to 1.00/100 patient-years in patients with MetS and MetS with impaired fasting glucose, respectively. Older age, increased waist circumference, and persistent MetS were determinants of NOD. One CVD nonfatal event occurred in the 28 patients with NOD. Our findings suggest that treating the characteristics of MetS is achievable and beneficial. New-onset diabetes incidence and CVD events were negligible and not different from what is expected in the general population.     

Activation of acetylcholinesterase after U-74389G administration in a porcine model of intracerebral hemorrhage

Spontaneous intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes. Despite high incidence, morbidity and mortality, the precise pathophysiology of spontaneous ICH is not fully understood, while there is little data concerning the mechanisms that follow the primary insult of the hematoma formation. The cholinergic system, apart from its colossal importance as a neurotransmission system, seems to also play an important role in brain injury recovery. It has been recently suggested that the brain possesses a cholinergic anti-inflammatory pathway that counteracts the inflammatory responses after ICH, thereby limiting damage to the brain itself. We, herein, report the findings of our study concerning the role of acetylcholinesterase (AChE; a crucial membrane-bound enzyme involved in cholinergic neurotransmission) in a porcine model of spontaneous ICH, with a focus on the first 4 and 24 h following the lesion’s induction, in combination with a study of the effectiveness of the lazaroid antioxidant U-74389G administration. Our study demonstrates the activation of AChE activity following U-74389G administration. The lazaroid U-74389G seems to be an established neuroprotectant and this is the first report of its supporting role in the enhancement of cholinergic response to the induction of ICH.     

Incidence,timing, and predictors of valve dislodgment during TAVI with the medtronic corevalve system

Objectives : To determine the incidence, timing and predictors of periprocedural valve dislodgment with the Medtronic Corevalve System (MCS). Background : Periprocedural valve dislodgment may occur during transcatheter aortic valve implantation (TAVI). Methods : Ninety‐eight consecutive patients underwent TAVI with the MCS after a comprehensive baseline assessment including invasive angiography, echocardiography, and Multi‐Slice Computed Tomography (MSCT). The invasive monitoring charts and angiographic studies of all TAVI procedures were reviewed to determine the incidence and timing of valve dislodgment. Results : Valve dislodgment occurred in 18 patients. Patients with valve dislodgment had a larger Aortic Valve Area (0.76 ± 0.25 cm² vs. 0.61 ± 0.19 cm², P = 0.007), lower mean transaortic gradient (37.65 ± 14.62 mm Hg vs. 47.11 ± 16.08 mm Hg, P = 0.03) and significantly less aortic root calcification (Agatston score median 1951 AU (IQR, 799–3103) vs. 3289 AU (IQR 2097–4481), P = 0.016). A lower aortic root calcium score (Agatston score < 2359 AU) was the single independent predictor for valve dislodgment (OR 3.10, 1.09–8.84). After valve dislodgment, the valve could be successfully retrieved and implanted in the proper anatomic location in all cases. Valve dislodgment was associated with a lower incidence of post‐procedural AR ≥ 2 (11.1% vs. 34.6%, P = 0.05). There were no relevant procedural or clinical implications to valve dislodgment. Conclusions : The incidence of periprocedural valve dislodgment was 18% in these series. Less aortic root calcification appeared the single independent predictor. © 2011 Wiley Periodicals, Inc.     

An exploratory, placebo-controlled, dose–response study of the efficacy and safety of onabotulinumtoxinA in spinal cord injury patients with urinary incontinence due to neurogenic detrusor overactivity

Purpose

To explore the dose response to onabotulinumtoxinA 50, 100, and 200 U in patients with spinal cord injury (SCI) with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO).

Methods

Patients (N = 73) with SCI (level T1 or lower) with NDO and UI (≥14 UI episodes/week) received 30 intradetrusor injections of onabotulinumtoxinA (50 U [n = 19], 100 U [n = 21], or 200 U [n = 17]) or placebo (n = 16) via cystoscopy, avoiding the trigone. Changes from baseline in UI episodes/week, volume voided/micturition, maximum cystometric capacity, and maximum detrusor pressure (MDP) during first involuntary detrusor contraction (IDC) were evaluated. Adverse events (AEs) were assessed.

Results

A significant linear dose response for UI episodes/week was identified at weeks 18, 30, 36, 42, and 54 (P < 0.05) with a similar trend (P = 0.092) at week 6 (primary time point). A significant linear dose response was observed in volume/void at all post-treatment time points up to week 54 (P < 0.05) and in MDP during first IDC at week 6 (P = 0.034). The proportion of patients who achieved continence at week 6 was highest in the 200 U group. Duration of effect was longest with the 200 U dose, compared with other treatment groups. The AEs were comparable across groups; urinary tract infection was the most common AE across all treatment groups.

Conclusions

In this exploratory dose–response study of SCI patients with UI due to NDO, onabotulinumtoxinA 200 U was the most effective dose. The AE profile was comparable across all groups.     

Complex calcaneal defect reconstruction with osteotomized free fibula–flexor hallucis longus osteomuscular flap

Complex calcaneal defects represent a reconstructive challenge since calcaneous plays a key role in standing and gait. We report the case of a 35‐year‐old patient with a complex calcaneal defect due to chronic osteomyelitis after a high energy Gustillo type IIIB calcaneal fracture that was reconstructed with a free fibula–flexor hallucis longus osteomuscular flap. The fibula was osteotomized into two segments, which were used to reconstruct the bone defect, and the muscular component of the flap was used for coverage of the reconstructed calcaneal skeleton. Fifteen days later permanent skin coverage was ensured with a local random pattern rhomboid skin flap. Early and late postoperative periods were uneventful. Bone maturation was radiographically evident at a follow up of 12 weeks, and complete bone incorporation at 3 years. Full weight bearing was possible at 6 months postop. Final follow up, at 3 years postop, verified a very good functional and aesthetic outcome. © 2012 Wiley Periodicals, Inc. Microsurgery, 2013.     

Subcutaneous drain insertion in patients with post-operative extensive subcutaneous surgical emphysema: a single centre experience

Objective

Extensive surgical subcutaneous emphysema (ESE) albeit a benign condition could cause patients distress and in many cases temporary vision impairment. We describe the role and value of early subcutaneous drain insertion (SCD) in the management of ESE and patients’ experience in this cohort study.

Methods

Extensive surgical subcutaneous emphysema is that which extends to the neck and/or the peri-orbital region. A cohort study of a prospectively collected data was conducted between December 2009 and January 2012. All patients with extensive post-operative surgical emphysema who had SCD (size ≥24 French gauge) were included.

Results

1069 thoracic procedures were performed. 21 patients (1.96 %) were diagnosed with extensive surgical emphysema, there were 16 males, median age was 65 (54–82 years). There were 16 VATS and 5 open procedures. All patients had chest surgical emphysema, 16 patients had peri-orbital and neck swelling and 5 had neck swelling. Surgical emphysema occurred within a median of 3 days post-operatively. 14 (67 %) patients had 1 subcutaneous drain inserted, and 7 (33 %) had bilateral SCD insertion (1 drain each side). 19 (90 %) patients experienced improvement of their symptoms with resolution of neck and peri-orbital swelling within 1 day of SCD insertion, 2 patients had their symptoms improved within 2 days. All patients were satisfied with the outcome following insertion of SCD.

Conclusions

ESE should always be investigated and treated promptly. Early SCD insertion has a valuable role in the management of ESE with improvement of patients’ experience.