Regional skeletal muscle perfusion distribution in diabetic feet may differentiate short-term healed foot ulcers from non-healed ulcers.

OBJECTIVES: The purpose of this study was to leverage a magnetic resonance imaging (MRI) approach to characterize foot perfusion distribution in patients with diabetes, with or without foot ulcers, and determine the ability of the regional perfusion measurements to identify ulcer-healing status. METHODS: Three groups of participants (n = 15 / group) were recruited: controls (without diabetes), type II diabetes, and type II diabetes with foot ulcers. All participants underwent MRI evaluating foot perfusion in three muscle layers (from plantar to dorsal) at rest and during a standardized toe-flexion exercise. The exercise perfusion and perfusion reserve values were analyzed around and away from ulcers. Participants with foot ulcers were followed up 3 months after the MRI exams to determine the foot healing status. RESULTS: Foot plantar muscle perfusion reserves were progressively lower from controls to diabetes, and to diabetes with foot ulcers (e.g., 2.58 ± 0.67, 1.48 ± 0.71, 1.12 ± 0.35, p < 0.001). In controls, the plantar layer had significantly higher perfusion reserve than the dorsal layer, whereas in either diabetes group, there was no significant difference in perfusion reserve among muscle layers. Using the ratio of total exercise perfusion around ulcers to that away from ulcers, the sensitivity and specificity to differentiate healing from non-healed ulcers were 100% and 86%, respectively. CONCLUSIONS: Our study reveals significantly different foot perfusion distribution among controls, diabetes, and diabetes with foot ulcers. The prognostic value of MRI regional perfusion assessments has the potential to monitor interventions to improve ulcer healing outcomes. KEY POINTS: • Contrast-free MRI permits quantitative assessment of regional foot muscle perfusion at rest and during isometric exercise. • Patients with diabetes and foot ulcers, without clinical evidence of peripheral arterial disease, had significantly impaired foot muscle perfusion and perfusion reserve. • Regional foot perfusion distribution may be used to predict the short-term healing status of foot ulcers in diabetes.

Transmembrane TNF-TNFR2 signaling as a critical immunoregulatory node in pancreatic cancer.

Pancreatic cancer is characterized by extreme therapeutic resistance. In pancreatic cancers harboring high-risk genomes, we describe that cancer cell-neutrophil signaling circuitry provokes neutrophil-derived transmembrane (tm)TNF-TNFR2 interactions that dictate inflammatory polarization in cancer-associated fibroblasts and T-cell dysfunction - two hallmarks of therapeutic resistance. Targeting tmTNF-TNFR2 signaling may sensitize pancreatic cancer to chemo±immunotherapy.

A case of spontaneous abdominal hemoperitoneum secondary to ruptured splenosis.

We present a case of spontaneous abdominal hemoperitoneum secondary to ruptured splenosis in a 35-year-old patient with a history of splenectomy secondary to trauma 23 years prior. Computed tomography imaging demonstrated a large amorphous mass-like structure in the mesentery of the left hemiabdomen with active extravasation and hemoperitoneum. The patient also had a separate focus of hyper-enhancing mass adjacent to the bladder representing a mass versus splenule. The patient's radiographic and clinical presentation prompted management with exploratory laparotomy, hematoma evacuation, and resection of two splenules. With only a few cases of spontaneous abdominal hemoperitoneum from splenosis reported, this case describes successful management with surgical intervention.

The evaluation of a PCR-based method for identification of Salmonella enterica serotypes from environmental samples and various food matrices.

The most commonly used method for serotyping Salmonella spp. is based on the Kaufmann-White scheme, and is composed of serological reactions using antibodies to LPS agglutinins. The multiplex PCR used in this investigation was established by Kim et al. to serotype the 30 most common clinical Salmonella serotypes, as determined by CDC. The PCR assay consists of two five-plex reactions and a single two-plex PCR reaction, based on six genetic loci from Salmonella enterica serotype Typhimurium and four loci from S. enterica serotype Typhi. In this investigation, we further evaluated the method for serotyping Salmonella spp. using a reference collection, environmental samples collected from a Mid-Atlantic region tomato farm study, four food matrices spiked with different Salmonella serotypes and a proficiency test. The PCR assay was first evaluated using DNA isolated from pure cultures of isolates obtained from various clinical and environmental samples, and then DNA isolated from broth cultures of food matrices of "Red round" and Roma tomatoes, Romaine lettuce, green onions and Serrano peppers spiked with serotypes Newport, Typhimurium, Javiana and Saintpaul, respectively. The results showed that the PCR assay correctly serotyped Salmonella spp. from the clinical, environmental, spiked food matrices, and proficiency test samples. These findings are significant because the PCR assay was successful in the identification of Salmonella in the spiked samples in a broth culture containing other non-salmonella organism. This method may be a useful resource for the food safety community.

Recovery of Salmonella from internally and externally contaminated whole tomatoes using several different sample preparation procedures.

Studies were conducted to determine the relative effectiveness of whole soak [current Bacteriological Analytical Manual-(BAM) Salmonella method], quarter, stomach, and blend methods for the recovery of Salmonella organisms from internally and externally contaminated tomatoes. Tomatoes were subjected to three inoculation methods: surface inoculation, internal inoculation by injection, and immersion with single Salmonella serovars. The inoculation levels ranged from 1 to 100 CFU/tomato for surface and injection inoculation or 1 to 100 CFU/mL for immersion inoculation. Tomatoes were held for 3 days after inoculation at 2-6 degrees C prior to initiation of analysis. Contaminated tomatoes were soaked, quartered, stomached, and blended in appropriate portions of Universal Pre-enrichment broth, and incubated for 24 h at 35 +/- 2 degrees C. The BAM Salmonella culture method was followed thereafter, and tomatoes were treated as a low-microbial-load food. The stomaching procedure was significantly (P < 0.05) more effective than the whole soak procedure for recovery of internalized Salmonella from tomatoes (by injection). The blending procedure was arithmetically superior to the stomaching procedure for detection of internalized Salmonella from tomatoes (by immersion). The blending procedure showed the same effectiveness as the whole soak procedure for the detection of Salmonella on tomato surfaces. Comparisons between test portion-to-broth ratios (weight to volume) showed that a 1:3 test portion-to-broth ratio had a better buffering capacity for blended tomatoes than a 1:1 test portion-to-broth ratio. It is recommended that the current whole soak BAM tomato sample preparation procedure be replaced with a blending procedure and a 1:3 test portion-to-broth ratio.

c-Fos expression associated with reinstatement of cocaine-seeking behavior by response-contingent conditioned cues.

The capability of cocaine cues to generate craving in cocaine-dependent humans, even after extended abstinence, is modeled in rats using cue reinstatement of extinguished cocaine-seeking behavior. We investigated neural activity associated with incentive motivational effects of cocaine cues using c-fos mRNA and Fos protein expression as markers. Unlike preceding studies, we used response-contingent presentation of discrete cues to elicit cocaine seeking. Rats were first trained to press a lever, resulting in cocaine reinforcement and light and tone cues. Rats then underwent extinction training, during which lever presses decreased. On the test day, rats either received response-contingent cocaine cues or received no cues. The cues reinstated extinguished cocaine-seeking behavior on the test day. In general, cue-elicited c-fos mRNA and protein expression were similar and both were enhanced in the prefrontal cortex, ventral tegmental area (VTA), dorsal striatum, and nucleus accumbens. Cues elicited more widespread Fos protein expression relative to our previous research in which cues were presented noncontingently without prior extinction training, including increases in the VTA, substantia nigra, ventral subiculum, and lateral entorhinal cortex. We also observed a correlation between cocaine-seeking behavior and Fos in the agranular insula (AgI) and basolateral amygdala (BLA). The findings suggest that connections between BLA and AgI play a role in cue-elicited incentive motivation for cocaine and that reinstatement of cocaine seeking by response-contingent cues activates a similar corticolimbic circuit as that observed with other modes of cue presentation; however, activation of midbrain and ventral hippocampal regions may be unique to reinstatement by response-contingent cues.

Region-specific involvement of AMPA/Kainate receptors in Fos protein expression induced by cocaine-conditioned cues.

This study investigated the effects of the AMPA/Kainate receptor antagonist, NBQX, on cue-elicited cocaine-seeking behavior and concomitant changes in Fos protein expression. After cocaine self-administration training, rats underwent 24 days of abstinence during which they were exposed daily either to the self-administration environment with response-contingent cues previously paired with cocaine infusions available (Extinction group) or to an alternate environment (No Extinction group). Subsequently, rats were tested for cocaine-seeking behavior (i.e., operant responses without cocaine reinforcement) elicited by the cocaine-associated cues after pretreatment with either vehicle or NBQX (10 mg/kg, IP). NBQX markedly attenuated cue-elicited cocaine-seeking behavior relative to vehicle pretreatment in the No Extinction group and also decreased cue-elicited Fos protein expression in a region-specific manner in the anterior cingulate and orbitofrontal cortices, basolateral amygdala, nucleus accumbens core, and dorsal caudate-putamen, suggesting involvement of AMPA glutamate systems in specific subregions of the neuronal circuitry activated by cocaine cues.