Inter‐individual differences in audio‐motor learning of piano melodies and white matter fiber tract architecture

Humans vary substantially in their ability to learn new motor skills. Here, we examined inter‐individual differences in learning to play the piano, with the goal of identifying relations to structural properties of white matter fiber tracts relevant to audio‐motor learning. Non‐musicians (n = 18) learned to perform three short melodies on a piano keyboard in a pure audio‐motor training condition (vision of their own fingers was occluded). Initial learning times ranged from 17 to 120 min (mean ± SD: 62 ± 29 min). Diffusion‐weighted magnetic resonance imaging was used to derive the fractional anisotropy (FA), an index of white matter microstructural arrangement. A correlation analysis revealed that higher FA values were associated with faster learning of piano melodies. These effects were observed in the bilateral corticospinal tracts, bundles of axons relevant for the execution of voluntary movements, and the right superior longitudinal fasciculus, a tract important for audio‐motor transformations. These results suggest that the speed with which novel complex audio‐motor skills can be acquired may be determined by variability in structural properties of white matter fiber tracts connecting brain areas functionally relevant for audio‐motor learning. Hum Brain Mapp 35:2483–2497, 2014. © 2013 Wiley Periodicals, Inc .     

A double-blind trial of high versus conventional dosages of gold salts for rheumatoid arthritis

In a double-blind study, patients were randomly selected for treatment using conventional doses (CD; 50 mg) or high doses (HD; 150 mg) of sodium aurothiomalate given weekly by injection. Twenty-three patients were assigned to the CD group and 24 to the HD group. Neither efficacy nor toxicity correlated with serum gold concentrations. Conventional doses were as efficacious as high doses with respect to both rapidity and degree of response. However, side effects were much more frequent and severe in the HD group. Thus there is no reason to recommend a 150 mg weekly dosage regimen.     

Burden and severity of children's hospitalizations by respiratory syncytial virus in Portugal, 2015–2018

BackgroundRespiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in young children and is of considerable burden on healthcare systems. Our study aimed to evaluate ALRI hospitalizations related to RSV in children in Portugal.MethodsWe reviewed hospitalizations potentially related to RSV in children aged <5 years from 2015 to 2018, using anonymized administrative data covering all public hospital discharges in mainland Portugal. Three case definitions were considered: (a) RSV‐specific, (b) (a) plus unspecified acute bronchiolitis (RSV‐specific & Bronchiolitis), and (c) (b) plus unspecified ALRI (RSV‐specific & ALRI).ResultsA total of 9697 RSV‐specific hospitalizations were identified from 2015 to 2018—increasing to 26 062 for RSV‐specific & ALRI hospitalizations—of which 74.7% were during seasons 2015/2016–2017/2018 (November–March). Mean hospitalization rates per season were, for RSV‐specific, RSV‐specific & Bronchiolitis, and RSV‐specific & ALRI, respectively, 5.6, 9.4, and 11.8 per 1000 children aged <5 years and 13.4, 22.5, and 25.9 in children aged <2 years. Most RSV‐specific hospitalizations occurred in healthy children (94.9%) and in children aged <2 years (96.3%). Annual direct costs of €2.4 million were estimated for RSV‐specific hospitalizations—rising to €5.1 million for RSV‐specific & ALRI—mostly driven by healthy children (87.6%).ConclusionRSV is accountable for a substantial number of hospitalizations in children, especially during their first year of life. Hospitalizations are mainly driven by healthy children. The variability of the potential RSV burden across case definitions highlights the need for a universal RSV surveillance system to guide prevention strategies.     

Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells

Imiquimod (IMQ), a synthetic agonist to Toll-like receptor (TLR) 7, is being successfully used for the treatment of certain skin neoplasms, but the exact mechanisms by which this compound induces tumor regression are not yet understood. While treating basal cell carcinoma (BCC) patients with topical IMQ, we detected, by immunohistochemistry, sizable numbers of both myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) within the inflammatory infiltrate. Surprisingly, peritumoral mDCs stained positive for perforin and granzyme B, whereas infiltrating pDCs expressed tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The biological relevance of this observation can be deduced from our further findings that peripheral blood-derived CD11c(+) mDCs acquired antiperforin and anti-granzyme B reactivity upon TLR7/8 stimulation and could use these molecules to effectively lyse major histocompatibility complex (MHC) class I(lo) cancer cell lines. The same activation protocol led pDCs to kill MHC class I-bearing Jurkat cells in a TRAIL-dependent fashion. While suggesting that mDCs and pDCs are directly involved in the IMQ-induced destruction of BCC lesions, our data also add a new facet to the functional spectrum of DCs, ascribing to them a major role not only in the initiation but also in the effector phase of the immune response.     

Synchronized navigation of current and prior studies using image registration improves radiologist’s efficiency

Purpose

The purpose of this study was to investigate how the use of multi-modal rigid image registration integrated within a standard picture archiving and communication system affects the efficiency of a radiologist while performing routine interpretations of cases including prior examinations.

Methods

Six radiologists were recruited to read a set of cases (either 16 neuroradiology or 14 musculoskeletal cases) during two crossover reading sessions. Each radiologist read each case twice, one time with synchronized navigation, which enables spatial synchronization across examinations from different study dates, and one time without. Efficiency was evaluated based upon time to read a case and amount of scrolling while browsing a case using Wilcoxon signed rank test.

Results

Significant improvements in efficiency were found considering either all radiologists simultaneously, the two sections separately and the majority of individual radiologists for time to read and for amount of scrolling. The relative improvement for each individual radiologist ranged from 4 to 32% for time to read and from 14 to 38% for amount of scrolling.

Conclusion

Image registration providing synchronized navigation across examinations from different study dates provides a tool that enables radiologists to work more efficiently while reading cases with one or more prior examinations.

     

Immunopathologic features of allergic contact dermatitis in humans: participation of plasmacytoid dendritic cells in the pathogenesis of the disease?

Contrary to our abundant knowledge about the sensitization phase of human contact hypersensitivity, little is known about the cell types orchestrating the effector phase. In order to address this issue, we phenotypically analyzed biopsies from 72 h epicutaneous patch test reactions (n=10) and normal human skin (n=5) for the presence of various leukocyte differentiation antigens. The inflammatory infiltrate was dominated by CD3+/CD4+ T cells with approximately 30% of the cells coexpressing CD25 and CTLA-4, a phenotype consistent with either activated effector or regulatory T cells. In our search for professional antigen-presenting cells, we were surprised to find not only sizeable numbers of CD1a+ dendritic cells and CD1c+ dendritic cells, but also of CD123+, CD45RA+, BDCA-2+, CLA+, and CD62L+ plasmacytoid dendritic cells. Although virtually absent in normal human skin, these cells were detectable already 6 h after hapten challenge and were often found in close proximity to CD56+ natural killer cells, indicative of a functional interaction between these cell types. The detailed knowledge of the cellular composition of the inflammatory infiltrate in allergic contact dermatitis and its kinetics should form the basis for the investigation of the immunologic and molecular events operative in the perpetuation and resolution of the eczematous response.     

Histologic evaluation of rat mammary tumor necrosis by interstitial Nd:YAG laser hyperthermia.

The extent of coagulative necrosis caused by interstitial laser hyperthermia was measured for different quantities of laser energy in a rat mammary tumor model. Continuous wave Nd:YAG laser at a power level of 5 W was focused onto a 600 mu diameter bare tip quartz fiber and placed inside a 19-gauge needle, which allowed the para-axial flow of normal saline at 1 cc/min. A microthermocouple soldered to the outside of the probe continuously provided the interstitial temperature. After the probe was inserted into the tumor, it was withdrawn as laser energy was administered at a rate sufficient to maintain the temperature within 42-45 degrees C. Tumors were excised after 48 hours, fixed in formalin, cut in 3 mm slices, and the coagulated surfaces measured microscopically. Laser fiber transmission loss was 1% per 1,000 J of laser energy and the average time required to coagulate 1 cc of tumor was 2 minutes. There was a statistically significant correlation between the volume of tumor necrosis and the level of laser irradiation (r = 0.71, P less than 0.001). It is concluded that the described technique is an efficient method of tumor coagulation by interstitial laser hyperthermia and proportionally larger volumes of necrosis are created with greater amounts of laser energy.     

Dermal toxicity of topical (-)epigallocatechin-3-gallate in BALB/c and SKH1 mice

(-)Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, inhibits experimental chemical and physical carcinogenesis, yet little toxicological data has been reported. Therefore, we performed studies on the dermal toxicity of EGCG applied in an ointment formulation in mice. Female BALB/c mice were dehaired with a topical depilatory and administered 75 microl EGCG in hydrophilic Ointment U.S.P. at three concentrations (10, 3, and 1%, all w/w) daily for 30 days. At the 10% concentration, gross toxicity was manifested by the formation of erythema and papular lesions by day 5. A 7% reduction in weight was observed by day 15. No toxicity was observed at the two lower concentrations or in the vehicle control group. Also, no toxicity was observed when mice were dehaired by shaving. This study was repeated in female SKH1 mice, an outbred hairless strain that does not require depilation. No toxicity was observed in the SKH1 mice, indicating that daily topical EGCG appears non-toxic in normal skin. However, use of topical depilatories may potentiate dermal toxicity of EGCG.     

Protection of fiber function by para-axial fluid flow in interstitial laser therapy of malignant tumors

In the past, interstitial laser therapy frequently has failed because of the damage to the bare fiber tip due to intense heat generated at the point of contact. Using a rat mammary tumor model, we describe a method of placing a 600 micron fiber inside a gauge 19 needle cannula after its insertion into the tumor. With this device continuous wave Nd:YAG laser is delivered to the target tumor while 0.9% saline flows para-axially into the tumor. Significant coagulation necrosis was induced with 500 joules at 5 watts, 100 seconds and 1 cc per minute of saline while the needle-fiber is pulled out of the tumor by 10 mm. The mean transmission loss after 500 joules was 2% in ten experiments. The tumor edema due to 1.5 ml of saline was transient. We conclude that successful hyperthermic coagulation necrosis by Nd:YAG laser can be achieved with minimal transmission loss by employing the above technique.