A Portable, Encapsulated Microbial Whole-Cell Biosensing System for the Detection of Bioavailable Copper (II) in Soil.

A portable, field deployable whole-cell biosensor was developed that can withstand the complex matrices of soil and requires minimal to no sample preparation to monitor bioavailable concentrations of the essential micronutrient copper (II). Conventional measurement of micronutrients is often complex, laboratory-based, and not suitable for monitoring their bioavailable concentration. To address this need, we developed a fluorescence based microbial whole-cell biosensing (MWCB) system encoding for a Cu2+-responsive protein capable of generating a signal upon binding to Cu2+. The sensing-reporting protein was designed by performing circular permutation on the green fluorescent protein (GFP) followed by insertion of a Cu2+ binding motif into the structure of GFP. The design included insertion of several binding motifs and creating plasmids that encoded the corresponding sensing proteins. The signal generated by the sensing-reporting protein is directly proportional to the concentration of Cu2+ in the sample. Evaluation of the resulting biosensing systems carrying these plasmids was performed prior to selection of the optimal fluorescence emitting Cu2+-binding protein. The resulting optimized biosensing system was encapsulated in polyacrylate-alginate beads and embedded in soil for detection of the analyte. Once exposed to the soil, the beads were interrogated to measure the fluorescence signal emitted by the sensing-reporting protein using a portable imaging device. The biosensor was optimized for detection of Cu2+ in terms of selectivity, sensitivity, matrix effects, detection limits, and reproducibility in both liquid and soil matrices. The limit of detection (LoD) of the optimized encapsulated biosensor was calculated as 0.27 mg/L and 1.26 mg/kg of Cu2+ for Cu2+ in solution and soil, respectively. Validation of the portable imaging tools as a potential biosensing device in the field was performed.

Type I IFN signaling blockade by a PASylated antagonist during chronic SIV infection suppresses specific inflammatory pathways but does not alter T cell activation or virus replication.

Chronic activation of the immune system in HIV infection is one of the strongest predictors of morbidity and mortality. As such, approaches that reduce immune activation have received considerable interest. Previously, we demonstrated that administration of a type I interferon receptor antagonist (IFN-1ant) during acute SIV infection of rhesus macaques results in increased virus replication and accelerated disease progression. Here, we administered a long half-life PASylated IFN-1ant to ART-treated and ART-naïve macaques during chronic SIV infection and measured expression of interferon stimulated genes (ISG) by RNA sequencing, plasma viremia, plasma cytokines, T cell activation and exhaustion as well as cell-associated virus in CD4 T cell subsets sorted from peripheral blood and lymph nodes. Our study shows that IFN-1ant administration in both ART-suppressed and ART-untreated chronically SIV-infected animals successfully results in reduction of IFN-I-mediated inflammation as defined by reduced expression of ISGs but had no effect on plasma levels of IL-1ß, IL-1ra, IL-6 and IL-8. Unlike in acute SIV infection, we observed no significant increase in plasma viremia up to 25 weeks after IFN-1ant administration or up to 15 weeks after ART interruption. Likewise, cell-associated virus measured by SIV gag DNA copies was similar between IFN-1ant and placebo groups. In addition, evaluation of T cell activation and exhaustion by surface expression of CD38, HLA-DR, Ki67, LAG-3, PD-1 and TIGIT, as well as transcriptome analysis showed no effect of IFN-I blockade. Thus, our data show that blocking IFN-I signaling during chronic SIV infection suppresses IFN-I-related inflammatory pathways without increasing virus replication, and thus may constitute a safe therapeutic intervention in chronic HIV infection.

Simultaneous Mapping of T1 and T2 Using Cardiac Magnetic Resonance Fingerprinting in a Cohort of Healthy Subjects at 1.5T.

BACKGROUND: Cardiac MR fingerprinting (cMRF) is a novel technique for simultaneous T1 and T2 mapping. PURPOSE: To compare T1 /T2 measurements, repeatability, and map quality between cMRF and standard mapping techniques in healthy subjects. STUDY TYPE: Prospective. POPULATION: In all, 58 subjects (ages 18-60). FIELD STRENGTH/SEQUENCE: cMRF, modified Look-Locker inversion recovery (MOLLI), and T2 -prepared balanced steady-state free precession (bSSFP) at 1.5T. ASSESSMENT: T1 /T2 values were measured in 16 myocardial segments at apical, medial, and basal slice positions. Test-retest and intrareader repeatability were assessed for the medial slice. cMRF and conventional mapping sequences were compared using ordinal and two alternative forced choice (2AFC) ratings. STATISTICAL TESTS: Paired t-tests, Bland-Altman analyses, intraclass correlation coefficient (ICC), linear regression, one-way analysis of variance (ANOVA), and binomial tests. RESULTS: Average T1 measurements were: basal 1007.4±96.5 msec (cMRF), 990.0±45.3 msec (MOLLI); medial 995.0±101.7 msec (cMRF), 995.6±59.7 msec (MOLLI); apical 1006.6±111.2 msec (cMRF); and 981.6±87.6 msec (MOLLI). Average T2 measurements were: basal 40.9±7.0 msec (cMRF), 46.1±3.5 msec (bSSFP); medial 41.0±6.4 msec (cMRF), 47.4±4.1 msec (bSSFP); apical 43.5±6.7 msec (cMRF), 48.0±4.0 msec (bSSFP). A statistically significant bias (cMRF T1 larger than MOLLI T1 ) was observed in basal (17.4 msec) and apical (25.0 msec) slices. For T2 , a statistically significant bias (cMRF lower than bSSFP) was observed for basal (-5.2 msec), medial (-6.3 msec), and apical (-4.5 msec) slices. Precision was lower for cMRF-the average of the standard deviation measured within each slice was 102 msec for cMRF vs. 61 msec for MOLLI T1 , and 6.4 msec for cMRF vs. 4.0 msec for bSSFP T2 . cMRF and conventional techniques had similar test-retest repeatability as quantified by ICC (0.87 cMRF vs. 0.84 MOLLI for T1 ; 0.85 cMRF vs. 0.85 bSSFP for T2 ). In the ordinal image quality comparison, cMRF maps scored higher than conventional sequences for both T1 (all five features) and T2 (four features). DATA CONCLUSION: This work reports on myocardial T1 /T2 measurements in healthy subjects using cMRF and standard mapping sequences. cMRF had slightly lower precision, similar test-retest and intrareader repeatability, and higher scores for map quality. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1 J. Magn. Reson. Imaging 2020;52:1044-1052.

Neurotransmitters: The Critical Modulators Regulating Gut-Brain Axis.

Neurotransmitters, including catecholamines and serotonin, play a crucial role in maintaining homeostasis in the human body. Studies on these neurotransmitters mainly revolved around their role in the "fight or flight" response, transmitting signals across a chemical synapse and modulating blood flow throughout the body. However, recent research has demonstrated that neurotransmitters can play a significant role in the gastrointestinal (GI) physiology. Norepinephrine (NE), epinephrine (E), dopamine (DA), and serotonin have recently been a topic of interest because of their roles in the gut physiology and their potential roles in GI and central nervous system pathophysiology. These neurotransmitters are able to regulate and control not only blood flow, but also affect gut motility, nutrient absorption, GI innate immune system, and the microbiome. Furthermore, in pathological states, such as inflammatory bowel disease (IBD) and Parkinson's disease, the levels of these neurotransmitters are dysregulated, therefore causing a variety of GI symptoms. Research in this field has shown that exogenous manipulation of catecholamine serum concentrations can help in decreasing symptomology and/or disease progression. In this review article, we discuss the current state-of-the-art research and literature regarding the role of neurotransmitters in regulation of normal GI physiology, their impact on several disease processes, and novel work focused on the use of exogenous hormones and/or psychotropic medications to improve disease symptomology. J. Cell. Physiol. 232: 2359-2372, 2017. © 2016 Wiley Periodicals, Inc.

Spectrophotometric analyses of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in water.

A simple and accurate spectrophotometric method for on-site analysis of royal demolition explosive (RDX) in water samples was developed based on the Berthelot reaction. The sensitivity and accuracy of an existing spectrophotometric method was improved by: replacing toxic chemicals with more stable and safer reagents; optimizing the reagent dose and reaction time; improving color stability; and eliminating the interference from inorganic nitrogen compounds in water samples. Cation and anion exchange resin cartridges were developed and used for sample pretreatment to eliminate the effect of ammonia and nitrate on RDX analyses. The detection limit of the method was determined to be 100 µg/L. The method was used successfully for analysis of RDX in untreated industrial wastewater samples. It can be used for on-site monitoring of RDX in wastewater for early detection of chemical spills and failure of wastewater treatment systems.

A randomized pilot study of a comprehensive postoperative exercise program compared with usual care following primary total hip arthroplasty in subjects less than 65 years of age: feasibility, selection of outcome measures and timing of assessment.

BACKGROUND: Total Hip Arthroplasty (THA) is being used more commonly in younger higher demand patients. The purpose of this randomized pilot study was to explore a) feasibility of comprehensive postoperative rehabilitation compared to usual care following primary THA in subjects <65 years, b) appropriate outcome measures including performance-based measures and c) timing of assessments. METHODS: 21 subjects who underwent primary THA were randomized to receive a three-month out-patient rehabilitation program (Intervention) or usual postoperative care (Control). Subjects were assessed preoperatively, six-weeks postoperatively (Pre-intervention) and four and 12 months postoperatively (Post-intervention). Self-report measures were the Western Ontario McMaster Osteoarthritis Index (WOMAC) and Rand 36-Item Health Survey (RAND-36). Performance-based measures included lower extremity strength, walking speed and endurance, and gait laboratory assessment. RESULTS: Ten Control and 11 Intervention subjects with an average age of 53.4 (SD9.3) years were randomized. All Intervention subjects completed the program without adverse effects. Although no statistically significantly results were reported, four months postoperatively, Intervention subjects had clinically important differences (CID) in strength compared with Control subjects. Walking endurance, WOMAC and RAND scores improved significantly with no CID noted between groups. Ten (48%) subjects reported a ceiling effect on the WOMAC (9 (43%) subjects on Pain; 1 (5%) subject on Function). No group CID were noted in gait measures. CONCLUSIONS: Our recommendations would be that performance-based strength measures should be considered for the primary outcome in this younger cohort. Because of the ceiling effects with WOMAC Pain, a different pain measure is indicated. Other more challenging functional performance-based tests should be considered such as a more prolonged endurance test. There is merit in one-year follow-up as strength improved after four months in both groups.

Analysis of ChatGPT publications in radiology: Literature so far.

OBJECTIVE: To perform a detailed qualitative and quantitative analysis of the published literature on ChatGPT and radiology in the nine months since its public release, detailing the scope of the work in the short timeframe. METHODS: A systematic literature search was carried out of the MEDLINE, EMBASE databases through August 15, 2023 for articles that were focused on ChatGPT and imaging/radiology. Articles were classified into original research and reviews/perspectives. Quantitative analysis was carried out by two experienced radiologists using objective scoring systems for evaluating original and non-original research. RESULTS: 51 articles were published involving ChatGPT and radiology/imaging dating from 26 Jan 2023 to the last article published on 14 Aug 2023. 23 articles were original research while the rest included reviews/perspectives or brief communications. For quantitative analysis scored by two readers, we included 23 original research and 17 non-original research articles (after excluding 11 letters as responses to previous articles). Mean score for original research was 3.20 out of 5 (across five questions), while mean score for non-original research was 1.17 out of 2 (across six questions). Mean score grading performance of ChatGPT in original research was 3.20 out of five (across two questions). DISCUSSION: While it is early days for ChatGPT and its impact in radiology, there has already been a plethora of articles talking about the multifaceted nature of the tool and how it can impact every aspect of radiology from patient education, pre-authorization, protocol selection, generating differentials, to structuring radiology reports. Most articles show impressive performance of ChatGPT which can only improve with more research and improvements in the tool itself. There have also been several articles which have highlighted the limitations of ChatGPT in its current iteration, which will allow radiologists and researchers to improve these areas.

Insights into Women's health: Exploring the vaginal microbiome, quorum sensing dynamics, and therapeutic potential of quorum sensing quenchers.

The vaginal microbiome is an important aspect of women's health that changes dynamically with various stages of the woman's life. Just like the gut microbiome, the vaginal microbiome can also be affected by pathologies that dramatically change the typical composition of native vaginal microorganisms. However, the mechanism as to how both vaginal endemic and gut endemic opportunistic microbes can express pathogenicity in vaginal polymicrobial biofilms is poorly understood. Quorum sensing is the cellular density-dependent bacterial and fungal communication process in which chemical signaling molecules, known as autoinducers, activate expression for genes responsible for virulence and pathogenicity, such as biofilm formation and virulence factor production. Quorum sensing inhibition, or quorum quenching, has been explored as a potential therapeutic route for both bacterial and fungal infections. By applying these quorum quenchers, one can reduce biofilm formation of opportunistic vaginal microbes and combine them with antibiotics for a synergistic effect. This review aims to display the relationship between the vaginal and gut microbiome, the role of quorum sensing in polymicrobial biofilm formation which cause pathology in the vaginal microbiome, and how quorum quenchers can be utilized to attenuate the severity of bacterial and fungal infections.

Engineered biosensors for the quorum sensing molecule 3,5-dimethyl-pyrazine-2-ol (DPO) reveal its presence in humans, animals, and bacterial species beyond Vibrio cholerae.

A biosensor was engineered to enable the study of the novel quorum sensing molecule (QSM), 3,5-dimethylpyrazin-2-ol (DPO), employed by Vibrio cholerae to regulate biofilm formation and virulence factor production. Investigations into bacterial quorum sensing (QS), a form of communication based on the production and detection of QSMs to coordinate gene expression in a population dependent manner, offer a unique window to study the molecular underpinnings of microbial behavior and host interactions. Herein, we report the construction of an engineered microbial whole-cell bioluminescent biosensing system that incorporates the recognition of the VqmA regulatory protein of Vibrio cholerae with the bioluminescent reporting signal of luciferase for the selective, sensitive, stable, and reproducible detection of DPO in a variety of samples. Importantly, using our newly developed biosensor our studies demonstrate the detection of DPO in rodent and human samples. Employing our developed biosensor should help enable elucidation of microbial behavior at the molecular level and its impact in health and disease.

Rapid isothermal point-of-care test for screening of SARS-CoV-2 (COVID-19).

Rapid on-site diagnosis of emerging pathogens is key for early identification of infected individuals and for prevention of further spreading in a population. Currently available molecular diagnostic tests are instrument-based whereas rapid antibody and antigen tests are often not sufficiently sensitive for detection in pre-symptomatic subjects. There is a need for rapid point of care molecular screening tests that can be easily adapted to emerging pathogens and are selective, sensitive, reliable in different settings around the world. We have developed a simple, rapid (<30 â€‹min), and inexpensive test for SARS-CoV-2 that is based on combination of isothermal reverse transcription recombinase polymerase amplification (RT-RPA) using modified primers and visual detection with paper-based microfluidics. Our test (CoRapID) is specific for SARS-CoV-2 (alpha to omicron variants) and does not detect other coronaviruses and pathogens by in silico and in vitro analysis. A two-step test protocol was developed with stable lyophilized reagents that reduces handling by using portable and disposable components (droppers, microapplicators/swabs, paper-strips). After optimization of assay components and conditions, we have achieved a limit of detection (LoD) of 1 copy/reaction by adding a blocking primer to the lateral flow assay. Using a set of 138 clinical samples, a sensitivity of 88.1% (P â€‹< â€‹0.05, CI: 78.2-93.8%) and specificity of 93.9% (P â€‹< â€‹0.05, CI: 85.4-97.6%) was determined. The lack of need for instrumentation for our CoRapID makes it an ideal on-site primary screening tool for local hospitals, doctors' offices, senior homes, workplaces, and in remote settings around the world that often do not have access to clinical laboratories.

Engineered cells as biosensing systems in biomedical analysis.

Over the past two decades there have been great advances in biotechnology, including use of nucleic acids, proteins, and whole cells to develop a variety of molecular analytical tools for diagnostic, screening, and pharmaceutical applications. Through manipulation of bacterial plasmids and genomes, bacterial whole-cell sensing systems have been engineered that can serve as novel methods for analyte detection and characterization, and as more efficient and cost-effective alternatives to traditional analytical techniques. Bacterial cell-based sensing systems are typically sensitive, specific and selective, rapid, easy to use, low-cost, and amenable to multiplexing, high-throughput, and miniaturization for incorporation into portable devices. This critical review is intended to provide an overview of available bacterial whole-cell sensing systems for assessment of a variety of clinically relevant analytes. Specifically, we examine whole-cell sensing systems for detection of bacterial quorum sensing molecules, organic and inorganic toxic compounds, and drugs, and for screening of antibacterial compounds for identification of their mechanisms of action. Methods used in the design and development of whole-cell sensing systems are also reviewed.

Functional outcomes for 2 years comparing hip resurfacing and total hip arthroplasty.

This prospective observational study of 499 patients with hip resurfacing and 255 patients with total hip arthroplasty compared outcomes for 2 years. We used propensity scores to identify matched cohorts of 118 patients with hip resurfacing and 118 patients with total hip arthroplasty. We used these cohorts to compare improvements in the Western Ontario and McMaster University (WOMAC) osteoarthritis index and Medical Outcomes Short-Form 36 physical function component (SF-36 PF) scores at 3 months and at 1 and 2 years postsurgery. Both groups demonstrated significant improvements from baseline in WOMAC and SF-36 PF. Improvements in SF-36 PF were greater for patients with hip resurfacing than for patients with total hip arthroplasty 1 and 2 years postsurgery; improvements in WOMAC were similar for both groups. The clinical significance of this observation needs further investigation.

Bacterial Quorum-Sensing Molecules in Serum: A Potential Tool for Crohn's Disease Management.

Crohn's disease (CD) is an idiopathic inflammatory condition of the gastrointestinal tract with the primary method of diagnosis and follow-up being colonoscopy. A disturbed host-microbiome interaction, including the presence of pathobionts, is implicated in initiation and perpetuation of inflammation. As such, we hypothesized that bacterial quorum-sensing (QS) molecules (QSMs), small molecules bacteria generate to regulate gene expression, would be elevated in patients with CD. We collected serum at the time of colonoscopy from patients with CD and healthy controls, determining through biosensors for QSMs that patients with CD had significantly elevated levels of QSMs in serum. Expansion of these studies may allow for QSM levels in serum to serve as a biomarker for intestinal inflammation in patients with CD.

Inflammasome-Regulated Pyroptotic Cell Death in Disruption of the Gut-Brain Axis After Stroke.

Approximately 50% of stroke survivors experience gastrointestinal complications. The innate immune response plays a role in changes to the gut-brain axis after stroke. The purpose of this study is to examine the importance of inflammasome-mediated pyroptosis in disruption of the gut-brain axis after experimental stroke. B6129 mice were subjected to a closed-head photothrombotic stroke. We examined the time course of inflammasome protein expression in brain and intestinal lysate using western blot analysis at 1-, 3-, and 7-days post-injury for caspase-1, interleukin-1ß, nod-like receptor protein 3 (NLRP3), and apoptosis speck-like protein containing a caspase-recruiting domain (ASC) and gasdermin-D (GSDMD) cleavage. In a separate group of mice, we processed brain tissue 24 and 72 h after thrombotic stroke for immunohistochemical analysis of neuronal and endothelial cell pyroptosis. We examined intestinal tissue for morphological changes and pyroptosis of macrophages. We performed behavioral tests and assessed gut permeability changes to confirm functional changes after stroke. Our data show that thrombotic stroke induces inflammasome activation in the brain and intestinal tissue up to 7-day post-injury as well as pyroptosis of neurons, cerebral endothelial cells, and intestinal macrophages. We found that thrombotic stroke leads to neurocognitive and motor function deficits as well as increased gut permeability. Finally, the adoptive transfer of serum-derived EVs from stroke mice into naive induced inflammasome activation in intestinal tissues. Taken together, these results provide novel information regarding possible mechanisms underlying gut complications after stroke and the identification of new therapeutic targets for reducing the widespread consequences of ischemic brain injury.

Microbial whole-cell biosensors: Current applications, challenges, and future perspectives.

Microbial Whole-Cell Biosensors (MWCBs) have seen rapid development with the arrival of 21st century biological and technological capabilities. They consist of microbial species which produce, or limit the production of, a reporter protein in the presence of a target analyte. The quantifiable signal from the reporter protein can be used to determine the bioavailable levels of the target analyte in a variety of sample types at a significantly lower cost than most widely used and well-established analytical instrumentation. Furthermore, the versatile and robust nature of MWCBs shows great potential for their use in otherwise unavailable settings and environments. While MWCBs have been developed for use in biomedical, environmental, and agricultural monitoring, they still face various challenges before they can transition from the laboratory into industrialized settings like their enzyme-based counterparts. In this comprehensive and critical review, we describe the underlying working principles of MWCBs, highlight developments for their use in a variety of fields, detail challenges and current efforts to address them, and discuss exciting implementations of MWCBs helping redefine what is thought to be possible with this expeditiously evolving technology.

Activity of deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma models: Defining molecular mechanisms of resistance.

Panobinostat (LBH589) is a highly potent deacetylase inhibitor that has demonstrated clinical efficacy in patients with advanced cutaneous T-cell lymphoma (CTCL). To gain a better understanding of the compound activity in this tumor type, we investigated the cellular and molecular effects of panobinostat using both in vitro and in vivo models of CTCL. All 4 tested CTCL cell lines exhibited very high sensitivity to panobinostat-induced growth inhibition. However, only 2 of 4 lines exhibited significant response to the cytotoxic activity of panobinostat. In a CTCL xenograft mouse tumor model, panobinostat treatment resulted in complete tumor regression. The difference in cell sensitivity to panobinostat-induced death enabled us to further investigate potential mechanisms responsible for tumor sensitivity or resistance. In CTCL cell lines that were insensitive to panobinostat-induced apoptosis, constitutively activated NF-kappaB and high levels of Bcl-2 were observed. Inhibition of Bcl-2 sensitized cells to the cytotoxic activity of panobinostat. Conversely, knockdown of Bax diminished the CTCL cell sensitivity. Interestingly, panobinostat could induce cytotoxicity in vorinostat-resistant CTCL cells by downregulating phosphorylated STAT3 and STAT5 proteins. These studies suggest distinct mechanisms responsible for resistance to different deacetylase inhibitors. We show that the intrinsic apoptotic signaling plays an essential role in mediating panobinostat anticancer activity. Moreover, cancer cell sensitivity to panobinostat treatment may be further improved by combination with inhibition of anti-apoptotic factors. These data provide preclinical support that panobinostat, as a single agent or in combination with other anticancer agents, is a promising therapy for CTCL.

Identification of a Signaling Mechanism by Which the Microbiome Regulates Th17 Cell-Mediated Depressive-Like Behaviors in Mice.

OBJECTIVE: Microbiota dysbiosis has been linked to major depressive disorder, but the mechanisms whereby the microbiota modulates mood remain poorly understood. The authors tested whether specific changes in the microbiome modulate depressive-like behaviors. METHODS: Stools from learned helpless, non-learned helpless, and non-shocked mice were analyzed by V4 16S RNA sequencing to identify gut bacteria associated with learned helplessness and to quantify the level of the quorum-sensing molecule autoinducer-2 (AI-2). T cells were analyzed by flow cytometry, and serum amyloid proteins (SAA) were analyzed by quantitative real-time polymerase chain reaction. Fecal transfer approach and administration of oleic acid and AI-2 were used to determine the effects of the microbiome and quorum-sensing molecules on depressive-like behaviors. RESULTS: Mice deficient in segmented filamentous bacteria (SFB) were resilient to the induction of depressive-like behavior, and were resensitized when SFB was reintroduced in the gut. SFB produces the quorum-sensing AI-2 and promotes the production of SAA1 and SAA2 by the host, which increases T helper 17 (Th17) cell production. Th17 cells were required to promote depressive-like behaviors by AI-2, as AI-2 administration did not promote susceptibility to depressive-like behaviors or SAA1 and SAA2 production in Th17-deficient mice after stress. Oleic acid, an AI-2 inhibitor, exhibited antidepressant properties, reducing depressive-like behavior, intestinal SAA1 and SAA2 production, and hippocampal Th17 cell accumulation. Stool samples from 10 people with current depressive symptoms and 10 matched healthy control subjects were analyzed as well. Patients with current major depressive disorder exhibited increased fecal interleukin 17A, SAA, and SFB levels. CONCLUSIONS: The study results reveal a novel mechanism by which bacteria alter mood.

Investigation of Microbiota Alterations and Intestinal Inflammation Post-Spinal Cord Injury in Rat Model.

Although there has been a significant amount of research focused on the pathophysiology of spinal cord injury (SCI), there is limited information on the consequences of SCI on remote organs. SCI can produce significant effects on a variety of organ systems, including the gastrointestinal tract. Patients with SCI often suffer from severe, debilitating bowel dysfunction in addition to their physical disabilities, which is of major concern for these individuals because of the adverse impact on their quality of life. Herein, we report on our investigation into the effects of SCI and subsequent antibiotic treatment on the intestinal tissue and microbiota. For that, we used a thoracic SCI rat model and investigated changes to the microbiota, proinflammatory cytokine levels, and bacterial communication molecule levels post-injury and gentamicin treatment for 7 days. We discovered significant changes, the most interesting being the differences in the gut microbiota beta diversity of 8-week SCI animals compared to control animals at the family, genus, and species level. Specifically, 35 operational taxonomic units were enriched in the SCI animal group and three were identified at species level; Lactobacillus intestinalis, Clostridium disporicum, and Bifidobacterium choerinum. In contrast, Clostridium saccharogumia was identified as depleted in the SCI animal group. Proinflammatory cytokines interleukin (IL)-12, macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor alpha were found to be significantly elevated in intestinal tissue homogenate 4 weeks post-SCI compared to 8-weeks post-injury. Further, levels of IL-1ß, IL-12, and MIP-2 significantly correlated with changes in beta diversity 8-weeks post-SCI. Our data provide a greater understanding of the early effects of SCI on the microbiota and gastrointestinal tract, highlighting the need for further investigation to elucidate the mechanism underlying these effects.

Quantitative perfusion imaging of neoplastic liver lesions: A multi-institution study.

We describe multi-institutional experience using free-breathing, 3D Spiral GRAPPA-based quantitative perfusion MRI in characterizing neoplastic liver masses. 45 patients (age: 48-72 years) were prospectively recruited at University Hospitals, Cleveland, USA on a 3 Tesla (T) MRI, and at Zhongshan Hospital, Shanghai, China on a 1.5 T MRI. Contrast-enhanced volumetric T1-weighted images were acquired and a dual-input single-compartment model used to derive arterial fraction (AF), distribution volume (DV) and mean transit time (MTT) for the lesions and normal parenchyma. The measurements were compared using two-tailed Student's t-test, with Bonferroni correction applied for multiple-comparison testing. 28 hepatocellular carcinoma (HCC) and 17 metastatic lesions were evaluated. No significant difference was noted in perfusion parameters of normal liver parenchyma and neoplastic masses at two centers (p = 0.62 for AF, 0.015 for DV, 0.42 for MTT for HCC, p = 0.13 for AF, 0.97 for DV, 0.78 for MTT for metastases). There was statistically significant difference in AF, DV, and MTT of metastases and AF and DV of HCC compared to normal liver parenchyma (p < 0.5/9 = 0.0055). A statistically significant difference was noted in the MTT of metastases compared to hepatocellular carcinoma (p < 0.001*10-5). In conclusion, 3D Spiral-GRAPPA enabled quantitative free-breathing perfusion MRI exam provides robust perfusion parameters.