Gut microbes, diet, and cancer Hullar, Meredith A J; Burnett-Hartman, Andrea N; Lampe, Johanna W
Cancer treatment and research,
01/2014, Letnik:
159
Journal Article, Book Chapter
Recenzirano
Odprti dostop
An expanding body of evidence supports a role for gut microbes in the etiology of cancer. Previously, the focus was on identifying individual bacterial species that directly initiate or promote ...gastrointestinal malignancies; however, the capacity of gut microbes to influence systemic inflammation and other downstream pathways suggests that the gut microbial community may also affect risk of cancer in tissues outside of the gastrointestinal tract. Functional contributions of the gut microbiota that may influence cancer susceptibility in the broad sense include (1) harvesting otherwise inaccessible nutrients and/or sources of energy from the diet (i.e., fermentation of dietary fibers and resistant starch); (2) metabolism of xenobiotics, both potentially beneficial or detrimental (i.e., dietary constituents, drugs, carcinogens, etc.); (3) renewal of gut epithelial cells and maintenance of mucosal integrity; and (4) affecting immune system development and activity. Understanding the complex and dynamic interplay between the gut microbiome, host immune system, and dietary exposures may help elucidate mechanisms for carcinogenesis and guide future cancer prevention and treatment strategies.
Objectives
The aim of this study was to see the effect of Er:YAG laser irradiation in dentine and compare this with its effect in enamel. The mechanism of crack propagation in dentine was emphasised ...and its clinical implications were discussed.
Materials and methods
Coronal sections of sound enamel and dentine were machined to 50-μm thickness using a FEI-Helios Plasma (FIB). The specimen was irradiated for 30 s with 2.94-μm Er:YAG laser radiation in a moist environment, using a sapphire dental probe tip, with the tip positioned 2 mm away from the sample surface. One of the sections was analysed as a control and not irradiated. Samples were analysed using the Zeiss Xradia 810 Ultra, which allows high spatial resolution, nanoscale 3D imaging using X-ray computed tomography (CT).
Results
Dentine: In the peritubular dentine, micro-cracks ran parallel to the tubules whereas in the inter-tubular region, the cracks ran orthogonal to the dentinal tubules. These cracks extended to a mean depth of approximately 10 μm below the surface. On the dentine surface, there was preferential ablation of the less mineralised intertubular dentine, and this resulted in an irregular topography associated with tubules.
Enamel: The irradiated enamel surface showed a characteristic ‘rough’ morphology suggesting some preferential ablation along certain microstructure directions. There appears to be very little subsurface damage, with the prismatic structure remaining intact.
Conclusions
A possible mechanism is that laser radiation is transmitted down the dentinal tubules causing micro-cracks to form in the dentinal tubule walls that tend to be limited to this region.
Clinical relevance
Crack might be a source of fracture as it represents a weak point and subsequently might lead to a failure in restorative dentistry.
This study used an emerging brain imaging technique, functional near-infrared spectroscopy (fNIRS), to investigate functional brain activation and connectivity that modulates sometimes traumatic pain ...experience in a clinical setting. Hemodynamic responses were recorded at bilateral somatosensory (S1) and prefrontal cortices (PFCs) from 12 patients with dentin hypersensitivity in a dental chair before, during, and after clinical pain. Clinical dental pain was triggered with 20 consecutive descending cold stimulations (32° to 0°C) to the affected teeth. We used a partial least squares path modeling framework to link patients’ clinical pain experience with recorded hemodynamic responses at sequential stages and baseline resting-state functional connectivity (RSFC). Hemodynamic responses at PFC/S1 were sequentially elicited by expectation, cold detection, and pain perception at a high-level coefficient (coefficients: 0.92, 0.98, and 0.99, P < 0.05). We found that the pain ratings were positively affected only at a moderate level of coefficients by such sequence of functional activation (coefficient: 0.52, P < 0.05) and the baseline PFC-S1 RSFC (coefficient: 0.59, P < 0.05). Furthermore, when the dental pain had finally subsided, the PFC increased its functional connection with the affected S1 orofacial region contralateral to the pain stimulus and, in contrast, decreased with the ipsilateral homuncular S1 regions (P < 0.05). Our study indicated for the first time that patients’ clinical pain experience in the dental chair can be predicted concomitantly by their baseline functional connectivity between S1 and PFC, as well as their sequence of ongoing hemodynamic responses. In addition, this linked cascade of events had immediate after-effects on the patients’ brain connectivity, even when clinical pain had already ceased. Our findings offer a better understating of the ongoing impact of affective and sensory experience in the brain before, during, and after clinical dental pain.
The objectives of this study were to determine the effects of dietary ractopamine HCl (RAC) on muscle fiber characteristics and electromyography (EMG) measures of finishing barrow exhaustion when ...barrows were subjected to increased levels of activity. Barrows ( = 34; 92 ± 2 kg initial BW) were assigned to 1 of 2 treatments: a conventional swine finishing diet containing 0 mg/kg ractopamine HCl (CON) or a diet formulated to meet the requirements of finishing barrows fed 10 mg/kg RAC (RAC+). After 32 d on feed, barrows were individually moved around a track at 0.79 m/s until subjectively exhausted. Wireless EMG sensors were affixed to the deltoideus (DT), triceps brachii lateral head (TLH), tensor fasciae latae (TFL), and semitendinosus (ST) muscles to measure median power frequency (MdPF) and root mean square (RMS) as indicators of action potential conduction velocity and muscle fiber recruitment, respectively. After harvest, samples of each muscle were collected for fiber type, succinate dehydrogenase (SDH), and capillary density analysis. Speed was not different ( = 0.82) between treatments, but RAC+ barrows reached subjective exhaustion earlier and covered less distance than CON barrows ( < 0.01). There were no treatment × muscle interactions or treatment effects for end-point MdPF values ( > 0.29). There was a treatment × muscle interaction ( = 0.04) for end-point RMS values. The RAC diet did not change end-point RMS values in the DT or TLH ( > 0.37); however, the diet tended to decrease and increase end-point RMS in the ST and TFL, respectively ( < 0.07). There were no treatment × muscle interactions for fiber type, SDH, or capillary density measures ( > 0.10). Muscles of RAC+ barrows tended to have less type I fibers and more capillaries per fiber ( < 0.07). Type I and IIA fibers of RAC+ barrows were larger ( < 0.07). Compared with all other muscles, the ST had more ( < 0.01) type IIB fibers and larger type I, IIA, and IIX fibers ( < 0.01). Type I, IIA, and IIX fibers of the ST also contained less SDH compared with the other muscles ( < 0.01). Barrows fed a RAC diet had increased time to subjective exhaustion due to loss of active muscle fibers in the ST, possibly due to fibers being larger and less oxidative in metabolism. Size increases in type I and IIA fibers with no change in oxidative capacity could also contribute to early exhaustion of RAC+ barrows. Overall, EMG technology can measure real-time muscle fiber loss to help explain subjective exhaustion in barrows.
The reproducibility crisis (or replication crisis) in biomedical research is a particularly existential and under-addressed issue in the field of behavioral neuroscience, where, in spite of efforts ...to standardize testing and assay protocols, several known and unknown sources of confounding environmental factors add to variance. Human interference is a major contributor to variability both within and across laboratories, as well as novelty-induced anxiety. Attempts to reduce human interference and to measure more "natural" behaviors in subjects has led to the development of automated home-cage monitoring systems. These systems enable prolonged and longitudinal recordings, and provide large continuous measures of spontaneous behavior that can be analyzed across multiple time scales. In this review, a diverse team of neuroscientists and product developers share their experiences using such an automated monitoring system that combines Noldus PhenoTyper
®
home-cages and the video-based tracking software, EthoVision
®
XT, to extract digital biomarkers of motor, emotional, social and cognitive behavior. After presenting our working definition of a “home-cage”, we compare home-cage testing with more conventional out-of-cage tests (e.g., the open field) and outline the various advantages of the former, including opportunities for within-subject analyses and assessments of circadian and ultradian activity. Next, we address technical issues pertaining to the acquisition of behavioral data, such as the fine-tuning of the tracking software and the potential for integration with biotelemetry and optogenetics. Finally, we provide guidance on which behavioral measures to emphasize, how to filter, segment, and analyze behavior, and how to use analysis scripts. We summarize how the PhenoTyper has applications to study neuropharmacology as well as animal models of neurodegenerative and neuropsychiatric illness. Looking forward, we examine current challenges and the impact of new developments. Examples include the automated recognition of specific behaviors, unambiguous tracking of individuals in a social context, the development of more animal-centered measures of behavior and ways of dealing with large datasets. Together, we advocate that by embracing standardized home-cage monitoring platforms like the PhenoTyper, we are poised to directly assess issues pertaining to reproducibility, and more importantly, measure features of rodent behavior under more ethologically relevant scenarios.
Aim
The effect of negative pressure wound therapy (NPWT) on the pathogenesis and outcome of enteroatmospheric fistulation (EAF) in the septic open abdomen (OA) is unclear. This study compares the ...development and outcome of EAF following NPWT with that occurring in the absence of NPWT.
Methods
Consecutive patients admitted with EAF following abdominal sepsis at a National Reference Centre for intestinal failure between 01 January 2005 and 31 December 2015 were included in this study. Patients were divided into two groups based on those that had been treated with NPWT and those that had not (non‐NPWT) and characteristics of their fistulas compared. Clinical outcomes concerning nutritional autonomy at 4 years and time to fistula development, size of abdominal wall defect and complete fistula closure were compared between groups.
Results
A total of 160 patients were admitted with EAF following a septic abdomen (31‐NPWT and 129‐non‐NPWT). Median (range) time taken to fistulation after OA was longer with NPWT (18 5–113 vs. 8 2–60 days, p = 0.004); these patients developed a greater number of fistulas (3 2–21 vs. 2 1–10, p = 0.01), involving a greater length of small bowel (42.5 15–100 cm vs. 30 3.5–170 cm, p = 0.04) than those who did not receive NPWT. Following reconstructive surgery, nutritional autonomy was similar in both groups (77% vs. 72%) and a comparable number of patients were also fistula‐free (100% vs. 97%).
Conclusions
Negative pressure wound therapy appears to be associated with more complex and delayed intestinal fistulation, involving a greater length of small intestine in the septic OA. This did not, however, appear to adversely affect the overall outcome of intestinal and abdominal wall reconstruction in this study.
Efforts to develop the next generation of aircraft with ever-increasing levels of performance – higher, farther, faster, cheaper – face great technical challenges. One of these technical challenges ...is to reduce structural weight of the aircraft. Another is to look to aircraft configurations that have been unrealizable to date. Both of these paths can lead to a rigid flex coupling phenomenon that can result in anything from poor flying qualities to the loss of an aircraft due to flutter. This has led to a need to develop an integrated flight and aeroelastic control capability where structural dynamics are included in the synthesis of flight control laws. Studies have indicated that the application of an integrated flight and aeroelastic control approach to a SensorCraft high-altitude long-endurance vehicle would provide substantial performance improvement(1,2). Better flying qualities and an expanded flight envelope through multi-flutter mode control are two areas of improvement afforded by integrated flight and aeroelastic control. By itself, multi-flutter mode control transforms the flutter barrier from a point of catastrophic structural failure to a benign region of flight. This paper discusses the history and issues associated with the development of such an integrated flight and aeroelastic control system for the X-56A aircraft.
The novel compound LY354740 is a conformationally constrained analog of glutamate, which was designed for interaction at metabotropic glutamate (mGlu) receptors. In this paper the selectivity of ...LY354740 for recombinant human mGlu receptor subtypes expressed in non-neuronal (RGT) cells is described. At human mGlu2 receptors, LY354740 produced > 90% suppression of forskolin-stimulated cAMP formation with an EC50 of 5.1 +/- 0.3 nM. LY354740 was six-fold less potent in activating human mGlu3 receptors (EC50 = 24.3 +/- 0.5 nM). LY354740 inhibition of forskolin-stimulated cAMP formation in human mGlu2 receptor-expressing cells was blocked by competitive mGlu receptor antagonists, including (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) and LY307452 ((2S,4S)-2-amino-4-(4,4-diphenylbut-1-yl)-pentane-1,5-dioic acid). LY354740 had no agonist or antagonist activities at cells expressing human mGlu4 or mGlu7 (group III mGlu receptors) (EC50 > 100,000 nM). When tested at group I phosphoinositide-coupled human mGlu receptors (mGlu1a and mGlu5a), LY354740 did not activate or inhibit mGlu receptor agonist-evoked phosphoinositide hydrolysis at up to 100,000 nM. Electrophysiological experiments also demonstrated that LY354740 also had no appreciable activity in cells expressing human recombinant AMPA (GluR4) and kainate (GluR6) receptors. Thus, LY354740 is a highly potent, efficacious and selective group II (mGlu2/3) receptor agonist, useful to explore the functions of these receptors in situ.
T zone lymphoma (TZL) is characterized by the clonal expansion of T cells lacking expression of the pan‐leukocyte antigen CD45 (TZ cells). A strong breed predisposition is observed in Golden ...retrievers. This study aimed to confirm aberrant CD45 mRNA expression and determine if Golden retrievers without clinical lymphoma have an increased frequency of circulating TZ cells. Gene expression analysis on confirmed TZL cases showed a significant decrease in CD45 expression compared to normal dogs. Peripheral blood samples from senior dogs, 242 Golden retrievers and 42 non‐Golden retrievers, without evidence of lymphoproliferative disease were assessed for the presence of TZ cells by flow cytometry. Thirty‐one percent of Golden retrievers had TZ cells compared to 14% of non‐Golden retrievers. Thirty‐four percent of Golden retrievers with TZ cells had a clonal T cell receptor gamma (TRG) gene rearrangement. Interestingly, 20% of Golden retrievers without TZ cells also had a clonal TRG rearrangement. Golden retrievers may have an increased risk of TZL due to an increased frequency of TZ cells.
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