Masked priming and ERPs dissociate maturation of orthographic and semantic components of visual word recognition in children

This study examined the time‐course of reading single words in children and adults using masked repetition priming and the recording of event‐related potentials. The N250 and N400 repetition priming effects were used to characterize form‐ and meaning‐level processing, respectively. Children had larger amplitude N250 effects than adults for both shorter and longer duration primes. Children did not differ from adults on the N400 effect. The difference on the N250 suggests that automaticity for form processing is still maturing in children relative to adults, while the lack of differentiation on the N400 effect suggests that meaning processing is relatively mature by late childhood. The overall similarity in the children's repetition priming effects to adults' effects is in line with theories of reading acquisition, according to which children rapidly transition to an orthographic strategy for fast access to semantic information from print.     

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.     

Glutathionyl hemoglobin is elevated in iron deficiency anemia

There are few good biomarkers of iron deficiency anemia (IDA). Since IDA patients have evidence for increased oxidative stress, we used mass spectrometry (MS) [i.e. matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization] to identify novel biomarkers. Using MALDI-MS, the following oxidative modifications of hemoglobin with the following mass-to-charge ratios were identified: 1,087.5 (α32-40), 1,545.7 (α17-31), 1,290.0 (β31-40) and 2,076.1 (β41-59). On electrospray ionization MS, the IDA patients had significantly elevated glutathionyl hemoglobin (GSHb) compared with the controls (16.9 ± 9.6 vs. 7.7 ± 3.7%; p = 0.002). GSHb levels correlated inversely with serum ferritin (Spearman rho -0.485; p = 0.003) and positively with serum transferrin receptor (0.460; p = 0.002). GSHb also demonstrated inverse correlations with hemoglobin (-0.512; p = 0.001), mean cell volume (-0.419; p = 0.026), serum iron (-0.446; p = 0.008) and transferrin saturation (-0.460; p = 0.008). For the first time, we show that GSHb is elevated in patients with IDA and has potential as a biomarker of this form of anemia.     

Bearing exchange in the management of pseudotumours

Introduction

Soft tissue reactions following metal-on-metal (MoM) arthroplasty of the hip have been under considerable discussion. These reactions are seen following both hip resurfacing and MoM total hip arthroplasty (THA). The phenomenon may arise owing to shedding of metal particles in high wear states, hypersensitivity with normal metal wear rates or a combination of the two.

Methods

Three patients were identified who had developed a soft tissue reaction (pseudotumour) following MoM hip resurfacing procedures. The prostheses were revised to ceramic-on-ceramic (CoC) THA with only minimal debridement of the pseudotumour. Pre and postoperative magnetic resonance imaging was performed to assess the size of the lesions.

Results

Progressive and satisfactory resolution of the associated pseudotumours was identified following revision of the prostheses to CoC THA.

Conclusions

In the early stages of pseudotumour formation following MoM hip resurfacing, this potentially devastating condition can be managed adequately with revision to a CoC bearing THA with minimal soft tissue excision.