'Functional' neuroanatomical tract tracing: analysis of changes in gene expression of brain circuits of interest

Neuroanatomical tracing when considered as an isolated method produces relatively straightforward answers. Although single-, double- or even triple-tracing paradigms produce valuable data on the organization of brain circuits, the final outcome often is too simplistic since it is not possible to elucidate the activity of these circuits. In this regard, emerging technologies contribute with additional information about the status of neuronal circuits. The laser-guided capture microdissection microscope (LCM) allows the accurate dissection of small brain areas under the microscope that could be further analyzed for gene expression or proteomics. In order to elucidate the gene expression of a given circuit of interest, we have developed a combination of methods comprising (i) fluorescent non-radioactive in situ hybridization for the detection of vGLUT2 mRNA expression combined with retrograde tracing with Fluoro-Gold (FG; analysis performed under the confocal microscope) and (ii) laser-guided capture microdissection of brain areas containing neurons retrogradely labeled with FG followed by the measurement of changes in mRNA levels encoding for vGLUT2 by real-time PCR. Our goal was to detect changes in gene expression of the thalamostriatal pathway in unilaterally 6-OHDA lesioned rats. Taking advantage of this procedure, we found a three-fold increase in vGLUT2 mRNA expression within thalamic neurons projecting to the dopamine-depleted striatum when compared with the activity of the thalamic neurons innervating the control striatum.     

The generalized quadratic knapsack problem. A neuronal network approach.

The solution of an optimization problem through the continuous Hopfield network (CHN) is based on some energy or Lyapunov function, which decreases as the system evolves until a local minimum value is attained. A new energy function is proposed in this paper so that any 0-1 linear constrains programming with quadratic objective function can be solved. This problem, denoted as the generalized quadratic knapsack problem (GQKP), includes as particular cases well-known problems such as the traveling salesman problem (TSP) and the quadratic assignment problem (QAP). This new energy function generalizes those proposed by other authors. Through this energy function, any GQKP can be solved with an appropriate parameter setting procedure, which is detailed in this paper. As a particular case, and in order to test this generalized energy function, some computational experiments solving the traveling salesman problem are also included.     

Relative localizing value of amygdalo-hippocampal MR biometry in temporal lobe epilepsy

OBJECTIVES: The aims of the study were (i) to examine the localizing value of three MRI quantitative modalities (qMRI) currently used for the analysis of the hippocampus and amygdala in the context of pre-surgical screening and (ii) to propose a step-by-step protocol based on the sensitivity and performance of the different MR techniques. METHODS: Ninety-two adults with chronic mesial temporal lobe epilepsy (TLE) of which 28 underwent amygdalo-hippocampal resection, and 34 age-matched controls were included in the study. High-resolution qMRI was performed at 1.5 T, including a tilted T1-weighted 3D-dataset for volumetry and four-echoes T2 relaxometry (both for hippocampus and amygdala quantifications) and multi-voxel spectroscopy [NAA/(Cho+Cre)] (exclusively in the hippocampus). Individual qMRI data were compared with electroencephalography regarding the localization of the epileptogenic area, with the neuropathological data and with postoperative outcome. MRI pathology was defined based on 99% confidence ellipses. Ten controls were used to assess the quantitative MRI intra- and inter-observer variability for all variables. RESULTS: Volumetric measurements revealed unilateral damage in 77% of the patients, T2-relaxometry in 64% and spectroscopy in 53%. Additional measurements of the amygdalae (T2-relaxometry) allowed us to localize pathology that coexists with that of the hippocampus in 34%, and isolated unilateral amygdala damage in 8% of patients. Volumetry and T2-relaxometry (not spectroscopy) were associated with postoperative outcome, but accurate predictive models were computed based on hippocampal measures only. At least at 1-year follow-up, volumetry predicts outcome correctly in 100% of the cases, whilst T2-relaxometry classified 96.4% (27/28) of these patients. All operated patients had hippocampal sclerosis. CONCLUSIONS: Hippocampal structural damage is equivocally depicted by spectroscopy. For diagnostic and pre-operative evaluation, hippocampal volumetry and T2-relaxometry provide maximal accuracy. Amygdala quantifications are irrelevant in the pre-operative evaluation but may be useful for diagnostic purposes. Of the three qMRI modalities tested, T2-relaxometry provided the best balance between diagnosis accuracy and time-efficiency to lateralize a sclerotic lesion on the majority of the patients. Cases that remain undecided after T2-relaxometry may benefit from additional measurements based on hippocampal volumetry.     

Spinal Posture of Thoracic and Lumbar Spine and Pelvic Tilt in Highly Trained Cyclists

The aim of this study was to evaluate sagittal thoracic and lumbar spinal curvatures and pelvic tilt in elite and master cyclists when standing on the floor, and sitting on a bicycle at three different handlebar-hand positions. A total of 60 elite male cyclists (mean age: 22.95 ± 3.38 years) and 60 master male cyclists (mean age: 34.27 ± 3.05 years) were evaluated. The Spinal Mouse system was used to measure sagittal thoracic and lumbar curvature in standing on the floor and sitting positions on the bicycle at three different handlebar-hand positions (high, medium, and low). The mean values for thoracic and lumbar curvatures and pelvic tilt in the standing position on the floor were 48.17 ± 8.05°, -27.32 ± 7.23°, and 13.65 ± 5.54°, respectively, for elite cyclists and 47.02 ± 9.24°, -25.30 ± 6.29°, and 11.25 ± 5.17° for master cyclists. A high frequency of thoracic hyperkyphosis in the standing position was observed (58.3% in elite cyclists and 53.3% in master cyclists), whereas predominately neutral values were found in the lumbar spine (88.3% and 76.7% in elite and master cyclists, respectively). When sitting on the bicycle, the thoracic curve was at a lower angle in the three handlebar-hand positions with respect to the standing position on the floor in both groups (p < 0.01). The lumbar curve adopted a kyphotic posture. In conclusion, cyclists present a high percentage of thoracic hyperkyphotic postures in standing positions on the floor. However, thoracic hyperkyphosis is not directly related to positions adopted on the bicycle.

Key points

• This study evaluated thoracic and lumbar spinal curvatures and pelvic tilt in elite and master cyclists while standing and sitting on the bicycle.
• Elite and master cyclists showed a high frequency of thoracic hyperkyphosis and neutral lumbar lordosis in standing.
• Cyclists adopted a significantly lower thoracic kyphosis on the bicycle at the three handlebar positions analysed (upper, middle and lower handlebars) than in standing posture. The lumbar spine showed a kyphotic posture.
• The high percentage of standing thoracic hyperkyphosis in both groups of cyclists may be related to factors other than the specific posture adopted while cycling. Lumbar kyphosis on the bicycle may not affect the sagittal configuration of the lumbar spine in standing.

     

Ascending-to-descending aortic bypass and aortic valve replacement for concomitant severe aortic coarctation and aortic stenosis

We present a 33-year-old male with severe, symptomatic aortic coarctation and aortic stenosis assessed on a humanitarian medical mission to a developing country. Contemplating limited time and available resources, we performed a simultaneous single-stage approach with ascending-to-descending aortic bypass with a reinforced gortex graft and concomitant aortic valve replacement through a median sternotomy. The patient had an uneventful postoperative convalescence and was discharged on postoperative day 5. At 1-year follow-up, he was asymptomatic and doing well with good blood pressure control and complete equalization of upper and lower limb blood pressure measurements. Computed tomography and transthoracic echocardiography demonstrated a widely patent ascending-to-descending aortic bypass graft and a normally functioning prosthetic aortic valve, respectively. In developing countries where health care resources are limited, a combined approach with an extra-anatomic, thoracic aortic bypass, and aortic valve replacement resulted in good early and 1-year outcomes. This procedure may represent the most effective surgical option for patients with concomitant aortic coarctation and aortic stenosis.     

Managing diabetic macular edema: The leading cause of diabetes blindness

Diabetic macular edema (DME) is the leading cause of blindness in young adults in developed countries, affecting 12% of type 1 and 28% of type 2 diabetic patients. The gold standard DME treatment should be based on a good control of glycemia along with control of lipids and renal function. However, despite the systemic metabolic control values being essential for patients with diabetic retinopathy (DR), it has proven to be insufficient for DME if it appears. With these patients, additional measures are needed in order to avoid the subsequent loss of vision. While laser treatment of DME has been the only valid treatment so far, it has been inadequate in chronic cases. The introduction of new treatments, such as intravitreal corticosteroids or anti-VEGF drugs, have recently shown their safety and efficacy and together with laser photocoagulation are becoming the treatments of choice in the management of DME.     

Atrial Myxoma and Bone Changes: A Paraneoplastic Syndrome?

Atrial myxomas are the most common benign tumors of the heart and are difficult to diagnose due to a wide variety of presenting symptoms. We present a patient with a five-year history of visual loss, vertigo, ataxia, tinnitus, and bone lesions that resolved after diagnosis and resection of an atrial myxoma. This case not only highlights an unusual presentation of atrial myxomas but also raises the question of whether atrial myxomas can produce paraneoplastic syndromes, including bone abnormalities.     

Early steroid withdrawal in pediatric renal transplant: five years of follow-up

This prospective, comparative trial investigated the impact on mean change in height standard deviation score (SDS), acute rejection rate, and renal function of early steroid withdrawal in 96 recipients with 5 years of follow-up. Recipients under basiliximab induction and steroid withdrawal (SW: TAC/MMF; n = 55) were compared with a matched steroid control group (SC: TAC/MMF/STEROID, n = 41). SW received steroids until Day 6, SC decreased to 10 mg/m(2) within 2 months post-transplant. Five years after SW, the longitudinal growth (SDS) gain was 1.4 ± 0.4 vs. 1.1 ± 0.3 for SC group (p < 0.02). Height benefits in prepubertal and pubertal status in both groups were demonstrated in the delta growth trends (mixed model; p < 0.01). Biopsy-proven acute rejection in SW was 11% and 17.5%, SC (p: ns). Mean eGFR (ml/min/1.73 m(2)) at 5 years post-transplant was SW 80.6 ± 27.8 vs. 82.6 ± 25.1 for SC (p: ns). The death-censored graft survival rate at 1 and 5 years was 99 and 90% for SW; 98 and 96% for SC (p = ns). PTLD incidence in SW 3.3 vs. 2.5% in SC (p: ns). Five years post-transplant, early steroid withdrawal showed positive impacts on growth, stable renal function without increased acute rejection risk, and PTLD incidence.     

Short PET in pediatric peritoneal dialysis

Peritoneal equilibration test (PET) is a common technique used in children to evaluate peritoneal membrane transport capacity and adequate the dialysis regimen. Considering that this is a laborious test, a shortened version has been proposed. Our goal was to evaluate the concordance between the 2-h (short) and 4-h (classical) PET values to determine whether the short PET could be used in the clinical setting. Eighty-one PET corresponding to 81 peritoneal dialysis patients from two pediatric nephrology centers were retrospectively analyzed. Peritoneal transport capacity was evaluated using the dialysate to plasma ratio (D/P) of creatinine and the ratio of dialysate glucose to baseline dialysate glucose (D/D(0)) at 2 and 4 h. The mean [+/- standard deviation (SD)] creatinine D/P ratio at 2 and 4 h were 0.41 +/- 0.13 and 0.66 +/- 0.17, respectively, and the mean (+/- SD) D/D(0) glucose were 0.64 +/- 0.11 and 0.39 +/- 0.12 at the same times. Applying McNemar chi(2) test to evaluate the association between the categories obtained at 2 and 4 h, we found no relationship between the 2- and 4-h PET for both D/P and D/D(0) (p > 0.05). These results suggest that the use of this abbreviated test is probably not reliable for estimating the transport capacity of the peritoneal membrane in the pediatric population.     

Evaluation of efficacy of four laparoscopic needle drivers.

INTRODUCTION: To evaluate the impact of needle driver design on laparoscopic suturing skills by experts and novices. METHODS: Three experienced laparoscopic surgeons and 3 novice junior residents were asked to perform a fixed set of suturing tasks in a laparoscopic pelvic-trainer. The laparoscopic needle drivers compared were (1) the Ethicon driver (E 705R), (2) Karl Storz (KS) pistol grip (26173 KC), (3) KS finger grip (26167 SK), and (4) KS palm grip (26173 ML). Times were recorded for each operator to grasp and position a needle for suturing in a particular angle, as well as to throw a horizontal and a vertical stitch and tie a single square knot using 2-0 Vicryl suture with a taper CT-1 needle. Subsequently, participants were asked to complete a subjective questionnaire rating the drivers. RESULTS: The average suturing time provided the most discriminatory power in comparing the needle drivers. For experienced operators, the KS pistol grip allowed faster suturing times than did the KS finger grip and the KS palm grip but not the Ethicon driver. For novice users, the Ethicon driver allowed faster suturing times than did the KS finger grip but not the KS pistol grip or the KS palm grip. In the subjective questionnaire, the KS pistol grip received the highest scores, and the KS finger grip received the lowest scores. CONCLUSION: Novice laparoscopists performed best with the KS pistol grip as well as the Ethicon laparoscopic needle drivers while experienced laparoscopists performed best with the pistol grip KS needle driver.