Hippocampal-prefrontal engagement and dynamic causal interactions in the maturation of children's fact retrieval

Children's gains in problem-solving skills during the elementary school years are characterized by shifts in the mix of problem-solving approaches, with inefficient procedural strategies being gradually replaced with direct retrieval of domain-relevant facts. We used a well-established procedure for strategy assessment during arithmetic problem solving to investigate the neural basis of this critical transition. We indexed behavioral strategy use by focusing on the retrieval frequency and examined changes in brain activity and connectivity associated with retrieval fluency during arithmetic problem solving in second- and third-grade (7- to 9-year-old) children. Children with higher retrieval fluency showed elevated signal in the right hippocampus, parahippocampal gyrus (PHG), lingual gyrus (LG), fusiform gyrus (FG), left ventrolateral PFC (VLPFC), bilateral dorsolateral PFC (DLPFC), and posterior angular gyrus. Critically, these effects were not confounded by individual differences in problem-solving speed or accuracy. Psychophysiological interaction analysis revealed significant effective connectivity of the right hippocampus with bilateral VLPFC and DLPFC during arithmetic problem solving. Dynamic causal modeling analysis revealed strong bidirectional interactions between the hippocampus and the left VLPFC and DLPFC. Furthermore, causal influences from the left VLPFC to the hippocampus served as the main top-down component, whereas causal influences from the hippocampus to the left DLPFC served as the main bottom-up component of this retrieval network. Our study highlights the contribution of hippocampal-prefrontal circuits to the early development of retrieval fluency in arithmetic problem solving and provides a novel framework for studying dynamic developmental processes that accompany children's development of problem-solving skills.     

Nanotechnology-novel therapeutics for CNS disorders

Research into treatments for diseases of the CNS has made impressive strides in the past few decades, but therapeutic options are limited for many patients with CNS disorders. Nanotechnology has emerged as an exciting and promising new means of treating neurological disease, with the potential to fundamentally change the way we approach CNS-targeted therapeutics. Molecules can be nanoengineered to cross the blood-brain barrier, target specific cell or signalling systems, respond to endogenous stimuli, or act as vehicles for gene delivery, or as a matrix to promote axon elongation and support cell survival. The wide variety of available nanotechnologies allows the selection of a nanoscale material with the characteristics best suited to the therapeutic challenges posed by an individual CNS disorder. In this Review, we describe recent advances in the development of nanotechnology for the treatment of neurological disorders-in particular, neurodegenerative disease and malignant brain tumours-and for the promotion of neuroregeneration.     

Stone measurement by volumetric three‐dimensional computed tomography for predicting the outcome after extracorporeal shock wave lithotripsy

OBJECTIVE

To evaluate the efficacy of stone volume measured using a three‐dimensional (3D) reconstruction of preoperative non‐contrast computed tomography (NCCT) as an independent predictor of success after extracorporeal shock wave lithotripsy (ESWL) of upper urinary tract calculi.

PATIENTS AND METHODS

We evaluated preoperative NCCT in 94 patients who had ESWL for solitary upper urinary tract calculi of 4–20 mm in diameter. Axial images were used to measure the skin‐to‐stone distance (SSD), Hounsfield Unit (HU) density and axial stone diameter. Stone volume was calculated on a volume‐rendered 3D image for each stone. Maximum stone length was determined by comparative measurements of each stone in coronal, sagittal and axial planes, and was also measured on a plain abdominal film before ESWL. For ESWL we used the DoliS lithotripter (Dornier Medical Systems, Marrietta, GA, USA). A plain film at 6 weeks was used to categorize patients as stone‐free (SF) or with residual stone.

RESULTS

In all, 58 (62%) patients were SF and 36 (38%) had RS; the mean stone volume was significantly different between these groups (274 vs 464 µL, P = 0.002). Logistic regression analysis showed that stone volume was the strongest predictor of SF status (P < 0.001), compared to peak HU (P = 0.015), mean HU (P = 0.04) and axial stone diameter (P = 0.006). The body mass index, SSD and maximum stone length on NCCT or a plain film did not predict success. A stone volume of <500 µL best predicted treatment success (P < 0.001) with 72% of patients with a stone volume of <500 µL having a successful outcome, vs only 27% with a stone volume of >500 µL.

CONCLUSION

Our study suggests that stone volume is an optimal predictor of SF status after ESWL of solitary upper urinary tract calculi.     

The combination of cyclophosphamide, velcade and dexamethasone induces high response rates with comparable toxicity to velcade alone and velcade plus dexamethasone

The combination of bortezomib (velcade), pulsed dexamethasone and weekly cyclophosphamide (CVD) in relapsed/refractory myeloma patients induces high overall (75%) and complete (31%) response rates compared to velcade/dexamethasone (overall 47%, CR 5%) and velcade alone (overall 27%, CR 0%). The toxicity profiles including thrombocytopenia, neutropenia, and neuropathy were comparable between the groups.     

Monteggia fracture-dislocations

Monteggia fracture-dislocations remain a relatively uncommon injury. Prompt recognition of this injury is imperative. The character of the ulnar fracture is useful in determining optimal treatment. It is imperative to look for associated injuries of the radial head and coronoid, which alter the management and lead to altered outcomes.     

The large and growing burden of stroke

Stroke is a disease with impacts ranging from death and disability, to reduced health-related quality of life and depression. To truly understand the burden of this disease we must investigate not only the mortality and prevalence of stroke, but also its incidence within populations. Stroke mortality and incidence declined rapidly during the 1980s and early 1990s; however, this trend appears to have slowed in more recent times. Despite many studies being conducted in Europe, and Australasia, there is a lack of reliable data from developing regions such as Asia and Africa. There are indications that although the mortality rate of stroke in such regions may be less than in developed countries, the simple fact that the populations are large means that the burden of stroke is considerable. Furthermore, as a result of epidemiological transition and rapid urbanization and industrialization many developing regions are exhibiting increased life expectancy, as well as changes in diet and other risk behaviors, such as smoking. This is contributing to a looming epidemic of stroke in these regions, as greater proportions of the population are now at risk of stroke. Fortunately, stroke is largely a preventable disease. The major risk factor for stroke, hypertension, can be controlled using both population-wide approaches, such as changes in the salt content of processed foods, and high-risk individual approaches, such as use of antihypertensive medications. Implementation of effective primary and secondary prevention strategies is likely to have an enormous benefit in reducing the burden of stroke, particularly in developing regions.     

Longitudinal monitoring of cardiac siderosis using cardiovascular magnetic resonance T2* in patients with thalassemia major on various chelation regimens: A 6‐year study

Cardiovascular magnetic resonance (CMR) and hepatic magnetic resonance imaging (MRI) have become reliable noninvasive tools to monitor iron excess in thalassemia major (TM) patients. However, long‐term studies are lacking. We reviewed CMR and hepatic MRI T2* imaging on 54 TM patients who had three or more annual measurements. They were managed on various chelation regimens. Patients were grouped according to their degree of cardiac siderosis: severe (T2*, <10 msec), mild to moderate (T2* = 10–20 msec), and no cardiac siderosis (T2*, >20 msec). We looked at the change in cardiac T2*, liver iron concentration (LIC) and left ventricular ejection fraction (LVEF) at years 3 and 5. In patients with severe cardiac siderosis, cardiac T2* (mean ± SD) improved from 6.9 ± 1.6 at baseline to 13.6 ± 10.0 by year 5, mean ΔT2* = 6.7 (P = 0.04). Change in cardiac T2* at year 3 was not significant in the severe group. Patients with mild to moderate cardiac siderosis had mean cardiac T2* of 14.6 ± 2.9 at baseline which improved to 26.3 ± 9.5 by year 3, mean ΔT2* = 11.7 (P = 0.01). At baseline, median LICs (mg/g dry weight) in patients with severe, mild–moderate, and no cardiac siderosis were 3.6, 2.8, and 3.3, whereas LVEFs (mean ± SD) (%) were 56.3 ± 10.1, 60 ± 5, and 66 ± 7.6, respectively. No significant correlation was noted between Δ cardiac T2* and Δ LIC, Δ cardiac T2*, and Δ LVEF at years 3 and 5. Throughout the observation period, patients with no cardiac siderosis maintained their cardiac T2* above 20 msec. The majority of patients with cardiac siderosis improve cardiac T2* over time with optimal chelation. Am. J. Hematol. 88:652–656, 2013. © 2013 Wiley Periodicals, Inc.     

A computable phenotype for asthma case identification in adult and pediatric patients: External validation in the Chicago Area Patient-Outcomes Research Network (CAPriCORN)

Objective: Comprehensive, rapid, and accurate identification of patients with asthma for clinical care and engagement in research efforts is needed. The original development and validation of a computable phenotype for asthma case identification occurred at a single institution in Chicago and demonstrated excellent test characteristics. However, its application in a diverse payer mix, across different health systems and multiple electronic health record vendors, and in both children and adults was not examined. The objective of this study is to externally validate the computable phenotype across diverse Chicago institutions to accurately identify pediatric and adult patients with asthma. Methods: A cohort of 900 asthma and control patients was identified from the electronic health record between January 1, 2012 and November 30, 2014. Two physicians at each site independently reviewed the patient chart to annotate cases. Results: The inter-observer reliability between the physician reviewers had a κ-coefficient of 0.95 (95% CI 0.93–0.97). The accuracy, sensitivity, specificity, negative predictive value, and positive predictive value of the computable phenotype were all above 94% in the full cohort. Conclusions: The excellent positive and negative predictive values in this multi-center external validation study establish a useful tool to identify asthma cases in in the electronic health record for research and care. This computable phenotype could be used in large-scale comparative-effectiveness trials.