Transcranial magnetic stimulation for migraine: a safety review.

OBJECTIVE: To review potential and theoretical safety concerns of transcranial magnetic stimulation (TMS), as obtained from studies of single-pulse (sTMS) and repetitive TMS (rTMS) and to discuss safety concerns associated with sTMS in the context of its use as a migraine treatment. METHODS: The published literature was reviewed to identify adverse events that have been reported during the use of TMS; to assess its potential effects on brain tissue, the cardiovascular system, hormone levels, cognition and psychomotor tests, and hearing; to identify the risk of seizures associated with TMS; and to identify safety issues associated with its use in patients with attached or implanted electronic equipment or during pregnancy. RESULTS: Two decades of clinical experience with sTMS have shown it to be a low risk technique with promise in the diagnosis, monitoring, and treatment of neurological and psychiatric disease in adults. Tens of thousands of subjects have undergone TMS for diagnostic, investigative, and therapeutic intervention trial purposes with minimal adverse events or side effects. No discernable evidence exists to suggest that sTMS causes harm to humans. No changes in neurophysiological function have been reported with sTMS use. CONCLUSIONS: The safety of sTMS in clinical practice, including as an acute migraine headache treatment, is supported by biological, empirical, and clinical trial evidence. Single-pulse TMS may offer a safe nonpharmacologic, nonbehavioral therapeutic approach to the currently prescribed drugs for patients who suffer from migraine.

Molecularly imprinted microgels as enzyme inhibitors.

We demonstrate, on the example of trypsin, the use of water-soluble molecularly imprinted polymer microgels as specific enzyme inhibitors. Using a strong anchoring monomer, methacryloylaminobenzamidine, the growing polymer chains are confined to close proximity of the substrate recognition site of our model enzyme. The microgels bind selectively trypsin over other proteins of similar size and molecular weight, and show competitive inhibition of trypsin with an inhibition constant K(i) of 79 nM, making them more potent inhibitors than the low molecular-weight competitive inhibitor benzamidine by almost 3 orders of magnitude. We believe that these tailor-made materials with biological activity have potential for future drug development that extends beyond enzyme inhibition.

Tissue Thickness Effects on Immunohistochemical Staining Intensity of Markers of Cancer.

High-quality patient samples are required for reliable immunohistochemistry test outcomes that provide a significant benefit for patient care. Among the preanalytic variables in tissue handling, tissue thickness is thought to be easily controlled; however, whether the thickness of the tissue effects the staining intensity for antibody immunohistochemistry has not been quantitatively demonstrated. To investigate, we cut multiblock tissue sections of tonsil, liver, and kidney at 2, 4, 6, and 8 µm thicknesses. Interferometry measurements of the sectioned paraffin showed a <1 µm variation within a preset microtome thickness. Sections were then immunostained with antibodies targeting different cellular localizations; Ki-67 and BCL6 (nuclear), CD7 (membranous), and cytokeratin (cytoplasmic). A pathologist annotated regions of interest for each marker and performed brightfield and whole-slide visual scoring. Then a pixel-wise processing algorithm determined intensity of each pixel in these regions of interest and binned them into predetermined 0, 1+, 2+, or 3+ intensities. Visual scores from brightfield and whole-slide images were highly correlated to the percentage of pixels in each intensity bin. A stepwise increase was observed in pathologist scores and algorithmically defined percentage of pixels in each bin with increasing thickness demonstrating that changes in preset section thickness impacts staining intensity. The use of tissue thickness outside vendors' recommendations might change the intensity including the proportion of positive and negative cells and eventually the overall diagnosis outcome. Therefore, we recommend that tissue be consistently cut within the middle of thickness range specified by the assay manufacturer.