We recently reported the development of a novel inhibitor of Rho-mediated gene transcription (1, CCG-203971) that is efficacious in multiple animal models of acute fibrosis, including scleroderma, when given intraperitoneally. The modest in vivo potency and poor pharmacokinetics (PK) of this lead, however, make it unsuitable for long term efficacy studies. We therefore undertook a systematic medicinal chemistry effort to improve both the metabolic stability and the solubility of 1, resulting in the identification of two analogs achieving over 10-fold increases in plasma exposures in mice. We subsequently showed that one of these analogs (8f, CCG-232601) could inhibit the development of bleomycin-induced dermal fibrosis in mice when administered orally at 50 mg/kg, an effect that was comparable to what we had observed earlier with 1 at a 4-fold higher IP dose.

We measured the specific resistances, 2ARPd∕Ag and 2ARPd∕Au (sample area A times resistance R), and spin-flip probabilities δPd∕Ag and δPd∕Au for Pd/Ag and Pd/Au interfaces with current perpendicular to the interfaces. 2ARPd∕Ag=0.7±0.15fΩm2 and 2ARPd∕Au=0.45±0.15fΩm2 are smaller than our revised estimate of 2ARPd∕Cu=0.85±0.15fΩm2, and lie further from no-free-parameter calculations. Our estimates of δPd∕Ag=0.15±0.08 and δPd∕Ag=0.08±0.08 are less than our prior estimate of δPd∕Cu∼0.24.

SUMMARY Symptoms of esophageal dysfunction such as food impaction are consistent with, but not diagnostic for eosinophilic esophagitis (EoE) without obtaining histology. We conducted a retrospective study to characterize patients with food impaction at a tertiary center. We hypothesized that many patients with food impaction may be lost to follow-up and that many have features suggestive of EoE. Adult patients presenting to the emergency department with esophageal food impaction were identified from an endoscopic database. Electronic medical records were manually abstracted. We examined associations between demographics, comorbid conditions, and follow-up with biopsy findings. Of 220 patients who presented to the emergency department for food impaction, 74.1% were men. Adequate follow-up was not documented in 120 (54.5%). Those lost to follow-up did not differ significantly by gender, age at symptom onset, or distance from hospital compared to those with follow-up. Esophageal biopsies were obtained in 158 (71.8%), and those with ≥15 eos/HPF were more likely to be lost to follow-up than those with <15 eos/HPF (52.8% vs. 34.8%, P < 0.05). Of those never biopsied, 79.0% were lost to follow-up and had intermediate proportions of males, food allergy, and asthma when compared to those with and without eosinophilic inflammation. Patients with food impaction commonly have EoE but are often lost to follow-up. Among those never biopsied, demographic and clinical features suggest that many may have undiagnosed EoE. Strategies for increasing use of biopsies in patients with food impaction and improving follow-up are needed to diagnose and manage EoE.

We compare specific resistances (AR = area A times resistance R) of sputtered Pd/Pt interfaces measured in two different ways with no-free-parameter calculations. One way gives 2AR Pd/Pt = 0.29 ± 0.03 fΩm 2 and the other 2AR Pd/Pt = 0.17 ± 0.13 fΩm 2 . From these we derive a 'best estimate' of 2AR Pd/Pt = 0.28 ± 0.06 fΩm 2 , which overlaps with no-free-parameters calculations: 2AR Pd/Pt (predicted) = 0.30 ± 0.04 fΩm 2 for flat, perfect interfaces, or 0.33 ± 0.04 fΩm 2 for interfaces composed of 2 monolayers of a 50%-50% PdPt Alloy. These results support three prior examples of agreement between calculations and measurements for pairs of metals having the same crystal structure and the same lattice parameter to within 1%. We also estimate the spin-flipping probability at Pd/Pt interfaces as δ Pd/Pt = 0.13 ± 0.08.

Wallenberg syndrome is the most common stroke of the posterior circulation. Diagnosis of Wallenberg syndrome is often overlooked as initial MRI may show no visible lesion. We present an atypical case of Wallenberg syndrome in which the initial MRI of the brain was normal.Our patient is a 65-year-old male who was brought in by emergency medical services complaining of rightsided facial droop, slurred speech, and left-sided weakness for one day. Physical examination showed decreased left arm and leg strength compared to the right side, decreased left facial temperature sensations, decreased left arm and leg temperature sensations, and difficulty sitting upright with an associated leaning towards the left side. An initial magnetic resonance imaging (MRI) of the brain with and without contrast revealed no abnormality. In light of such a high suspicion for stroke based on the patient's neurologic deficits, a repeat MRI of the brain was performed three days later and exposed a small focus of bright signal (hyperintensity) on T2-weighted fluid-attenuated inversion recovery and diffusion-weighted imaging (DWI) in the left posterior medulla.Wallenberg syndrome, also known as lateral medullary syndrome or posterior inferior cerebellar artery syndrome, is a constellation of symptoms caused by posterior vascular accidents. The neurological deficits associated with this disease are due to damage of the lateral medulla, inferior cerebellar peduncle, nucleus of trigeminal nerve, nucleus and fibers of vagus and glossopharyngeal nerves, descending sympathetic tract, spinothalamic tract, and/or vestibular nuclei. MRI with DWI is the gold standard to confirm the diagnosis.Wallenberg syndrome has the potential to leave patients extremely debilitated. Early detection, management, and rehabilitation are critical for improving post-stroke recovery.