Excess nutrition causes loss of olfactory sensory neurons (OSNs) and reduces odour discrimination and odour perception in mice. To separate diet‐induced obesity from the consumption of dietary fat, ...we designed pair‐feeding experiments whereby mice were maintained on isocaloric diets for 5 months, which prevented increased fat storage. To test our hypothesis that adiposity was not a prerequisite for loss of OSNs and bulbar projections, we used male and female mice with an odorant receptor‐linked genetic reporter (M72tauLacZ; Olfr160) to visualize neural circuitry changes resulting from elevated fat in the diet. Simultaneously we monitored glucose clearance (diagnostic for prediabetes), body fat deposition, ingestive behaviours, select inflammatory markers and energy metabolism. Axonal projections to defined olfactory glomeruli were visualized in whole‐mount brains, and the number of OSNs was manually counted across whole olfactory epithelia. After being pair fed a moderately high‐fat (MHF) diet, mice of both sexes had body weight, adipose deposits, energy expenditure, respiratory exchange ratios and locomotor activity that were unchanged from control‐fed mice. Despite this, they were still found to lose OSNs and associated bulbar projections. Even with unchanged adipocyte storage, pair‐fed animals had an elevation in TNF cytokines and an intermediate ability for glucose clearance. Albeit improving health metrics, access to voluntary running while consuming an ad libitum fatty diet still precipitated a loss of OSNs and associated axonal projections for male mice. Our results support that long‐term macronutrient imbalance can drive anatomical loss in the olfactory system regardless of total energy expenditure.
Key points
Obesity can disrupt the structure and function of organ systems, including the olfactory system that is important for food selection and satiety.
We designed dietary treatments in mice such that mice received fat, but the total calories provided were the same as in control diets so that they would not gain weight or increase adipose tissue.
Mice that were not obese but consumed isocaloric fatty diets still lost olfactory neuronal circuits, had fewer numbers of olfactory neurons, had an elevation in inflammatory signals and had an intermediate ability to clear glucose (prediabetes).
Mice were allowed access to running wheels while consuming fatty diets, yet still lost olfactory structures.
We conclude that a long‐term imbalance in nutrition that favours fat in the diet disrupts the olfactory system of mice in the absence of obesity.
figure legend Patterns of long‐term dietary consumption and exercise shape neuronal abundance and communication in the olfactory system. Design made in BioRender.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Neuromodulation influences neuronal processing, conferring neuronal circuits the flexibility to integrate sensory inputs with behavioral states and the ability to adapt to a continuously changing ...environment. In this original research report, we broadly discuss the basis of neuromodulation that is known to regulate intrinsic firing activity, synaptic communication, and voltage-dependent channels in the olfactory bulb. Because the olfactory system is positioned to integrate sensory inputs with information regarding the internal chemical and behavioral state of an animal, how olfactory information is modulated provides flexibility in coding and behavioral output. Herein we discuss how neuronal microcircuits control complex dynamics of the olfactory networks by homing in on a special class of local interneurons as an example. While receptors for neuromodulation and metabolic peptides are widely expressed in the olfactory circuitry, centrifugal serotonergic and cholinergic inputs modulate glomerular activity and are involved in odor investigation and odor-dependent learning. Little is known about how metabolic peptides and neuromodulators control specific neuronal subpopulations. There is a microcircuit between mitral cells and interneurons that is comprised of deep-short-axon cells in the granule cell layer. These local interneurons express pre-pro-glucagon (PPG) and regulate mitral cell activity, but it is unknown what initiates this type of regulation. Our study investigates the means by which PPG neurons could be recruited by classical neuromodulators and hormonal peptides. We found that two gut hormones, leptin and cholecystokinin, differentially modulate PPG neurons. Cholecystokinin reduces or increases spike frequency, suggesting a heterogeneous signaling pathway in different PPG neurons, while leptin does not affect PPG neuronal firing. Acetylcholine modulates PPG neurons by increasing the spike frequency and eliciting bursts of action potentials, while serotonin does not affect PPG neuron excitability. The mechanisms behind this diverse modulation are not known, however, these results clearly indicate a complex interplay of metabolic signaling molecules and neuromodulators that may fine-tune neuronal microcircuits.
In order to investigate the role of absorption in active galactic nuclei (AGN) with jets, we have studied the column density distribution of a hard X-ray selected sample of radio galaxies, derived ...from the INTEGRAL/Imager on Board the Integral Satellite (IBIS) and Swift/The Burst Alert Telescope (BAT) AGN catalogues (∼7–10 per cent of the total AGN population). The 64 radio galaxies have a typical FR II radio morphology and are characterized by high 20–100 keV luminosities (from 1042 to 1046 erg s−1) and high Eddington ratios (log L
Bol/L
Edd typically larger than ∼0.01). The observed fraction of absorbed AGN (N
H > 1022 cm−2) is around 40 per cent among the total sample, and ∼75 per cent among type 2 AGN. The majority of obscured AGN are narrow-line objects, while unobscured AGN are broad-line objects, obeying to the zeroth-order predictions of unified models. A significant anti-correlation between the radio core dominance parameter and the X-ray column density is found. The observed fraction of Compton thick AGN is ∼2–3 per cent, in comparison with the 5–7 per cent found in radio-quiet hard X-ray selected AGN. We have estimated the absorption and Compton thick fractions in a hard X-ray sample containing both radio galaxies and non-radio galaxies and therefore affected by the same selection biases. No statistical significant difference was found in the absorption properties of radio galaxies and non-radio galaxies sample. In particular, the Compton thick objects are likely missing in both samples and the fraction of obscured radio galaxies appears to decrease with luminosity as observed in hard X-ray non-radio galaxies.
Narrow-line Seyfert 1 galaxies at hard X-rays Panessa, F.; De Rosa, A.; Bassani, L. ...
Monthly Notices of the Royal Astronomical Society,
11/2011, Volume:
417, Issue:
4
Journal Article
Peer reviewed
Open access
Narrow-line Seyfert 1 (NLSy1) galaxies are a peculiar class of type 1 active galactic nuclei (broad-line Seyfert 1 galaxies, hereinafter BLSy1). The X-ray properties of individual objects belonging ...to this class are often extreme and associated with accretion at high Eddington ratios. Here, we present a study on a sample of 14 NLSy1 galaxies selected at hard X-rays (>20 keV) from the fourth INTEGRAL/IBIS catalogue. The 20-100 keV IBIS spectra show hard-X-ray photon indices flatly distributed (Γ20−100 keV ranging from ∼1.3 to ∼3.6) with an average value of 〈Γ20−100 keV〉= 2.3 ± 0.7, compatible with a sample of hard-X-ray BLSy1 average slopes. Instead, NLSy1 galaxies show steeper spectral indices with respect to BLSy1 galaxies when broad-band spectra are considered. Indeed, we combine XMM-Newton and Swift/XRT with INTEGRAL/IBIS data sets to obtain a wide energy spectral coverage (0.3-100 keV). A constraint on the high energy cut-off and on the reflection component is achieved only in one source, SWIFT J2127.4+5654 (E
cut-off∼ 50 keV, R= 1.0+0.5
− 0.4). Hard-X-ray-selected NLSy1 galaxies do not display particularly strong soft excess emission, while absorption fully or partially covering the continuum is often measured as well as Fe line emission features. Variability is a common trait in this sample, both at X-rays and at hard X-rays. The fraction of NLSy1 galaxies in the hard-X-ray sky is likely to be ∼15 per cent, in agreement with estimates derived in optically selected NLSy1 samples. We confirm the association of NLSy1 galaxies with small black hole masses with a peak at 107 M⊙ in the distribution; however, hard-X-ray NLSy1 galaxies seem to occupy the lower tail of the Eddington ratio distribution of classical NLSy1 galaxies.
The INTEGRAL/IBIS AGN catalogue: an update Malizia, A; Landi, R; Molina, M ...
Monthly notices of the Royal Astronomical Society,
07/2016, Volume:
460, Issue:
1
Journal Article
Peer reviewed
In the most recent IBIS survey based on observations performed during the first 1000 orbits of INTEGRAL, are listed 363 high-energy emitters firmly associated with AGN, 107 of which are reported here ...for the first time. We have used X-ray data to image the IBIS 90 per cent error circle of all the AGN in the sample of 107, in order to obtain the correct X-ray counterparts, locate them with arcsec accuracy and therefore pinpoint the correct optical counterparts. This procedure has led to the optical and spectral characterization of the entire sample. This new set consists of 34 broad line or type 1 AGN, 47 narrow line or type 2 AGN, 18 blazars and 8 sources of unknown class. These eight sources have been associated with AGN from their positional coincidence with 2MASX/Radio/X-ray sources. Seven high-energy emitters have been included since they are considered to be good AGN candidates. Spectral analysis has been already performed on 55 objects and the results from the most recent and/or best statistical measurements have been collected. For the remaining 52 sources, we report the spectral analysis for the first time in this work. We have been able to obtain the full X-ray coverage of the sample making use of data from Swift/XRT, XMM–Newton
and NuSTAR. In addition to the spectral characterization of the entire sample, this analysis has enabled us to identify peculiar sources and by comparing different data sets, highlight flux variability in the 2–10 keV and 20–40 keV bands.
Summary
Background
Psoriasis is an emerging paradoxical side effect in patients with inflammatory bowel disease (IBD) when treated with anti‐TNF alpha. Patients with severe skin lesions unresponsive ...to topical therapy need to withdraw from treatment.
Aim
To estimate the incidence of paradoxical psoriasis in a large cohort of IBD patients treated with anti‐TNF alpha and to analyse its clinical correlates.
Methods
A retrospective cohort study on all IBD patients who started anti‐TNF alpha at our IBD Centre from January 2008 to December 2013 was performed. Proportional hazards regression models were used to estimate the association between each predictor and time to the development of psoriasis. Time‐dependent predictors were updated at each available time point.
Results
Four hundred and two patients were included. Participants contributed a total of 839 person‐years of follow‐up, during which 42 incident cases of psoriasis were recorded, with an incidence rate of five per 100 person‐years. Cox‐regression survival analysis revealed smoking as independent predictor of psoriasis (HR: 2.37, 95% CI: 1.36–4.48; P = 0.008). Conversely, concomitant immunosuppressive therapy was inversely related to psoriasis (HR: 0.33, 95% CI: 0.12–0.92; P = 0.03).
Conclusions
Paradoxical psoriasis is a relevant side effect of anti‐TNF alpha therapy, with an incidence rate of five per 100 person‐years. Smoking is confirmed as the main risk factor for developing lesions. The combination therapy with anti‐TNF alpha plus immunosuppressants is associated with a reduced risk of paradoxical psoriasis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
In this paper we report on the broad-band X-ray properties of a complete sample of absorbed Seyfert galaxies hard X-ray selected with INTEGRAL. Our sample is composed of 33 sources, of which 15 are ...newly discovered active galactic nuclei (AGN) above 20 keV (IGR sources), while 18 are already known type 2 AGN ('known'). For 17 sources (15 IGR + 2 'known' sources) we have performed a broad-band analysis using both XMM-Newton, and INTEGRAL-IBIS data. To have a full view of the complete sample we have then complemented the analysis of the 16 remaining sources with already existing broad-band studies in the same range. The high-quality broad-band spectra are well reproduced with an absorbed primary emission with a high-energy cut-off and its scattered fraction below 2-3 keV, plus the Compton reflection features (Compton hump and Fe line emission). This study permitted a very good characterization of the primary continuum and, in turn, of all the spectral features.
A high-energy cut-off is found in 30 per cent of the sample, with an average value below 150 keV, suggesting that this feature has to be present in the X-ray spectra of obscured AGN. The hard X-ray selection favours the detection of more obscured sources, with the log N
H average value of 23.15 (standard deviation of 0.89). The diagnostic plot N
H versus F
oss(2-10 keV)/F(20-100 keV) allowed the isolation of the Compton-thick objects, and may represent a useful tool for future hard X-ray observations of newly discovered AGN. We are unable to associate the reflection components (both continuum and Fe line) with the absorbing gas as a torus (as envisaged in the Unified Model), a more complex scenario being necessary. In the Compton-thin sources, a fraction (but not all) of the Fe K line needs to be produced in a gas located closer to the black hole than the Compton-thick torus, and this is possibly associated with the optical broad-line region, responsible also for the absorption. We still need a Compton-thick medium (not intercepting the line of sight) likely associated to a torus, which contributes to the Fe line intensity and produces the observed reflection continuum above 10 keV. The so-called Iwasawa-Taniguchi effect cannot be confirmed with our data. Finally, the comparison with a sample of unobscured AGN shows that type 1 and type 2 (once corrected for absorption) Seyfert are characterized by the same nuclear/accretion properties (luminosity, bolometric luminosity, Eddington ratio), supporting the 'unified' view.
Abstract
The latest INTEGRAL/IBIS all-sky survey lists 219 hard X-ray sources whose nature is still unknown. We report on our ongoing campaign aimed at identifying these high-energy emitters by ...exploiting the focusing capabilities of the X-ray Telescope (XRT, 0.2–10 keV) onboard Swift, which allow an enhancement of the source localization to arcsec level, thus facilitating the identification of the likely counterpart. By cross-correlating the list of the unidentified IBIS sources included in the latest IBIS catalogue with Swift/XRT archival data, we found a set of 14 objects, not yet reported in the literature, for which XRT data were available. We found no detection in only one case, a single X-ray association in nine sources and 2/3 associations in the remaining objects. We then made use of multiwaveband archives to search for counterparts at other wavelengths of these XRT detections and exploited X-ray spectral information in an attempt to determine their nature and association with the IBIS object. As a result of our analysis, we identified a single counterpart for 13 sources, although in some cases its nature/class could not be assessed on the basis of the information collected. More specifically, we found that SWIFT J0924.2−3141 and SWIFT J1839.1−5717 are absorbed AGN, while SWIFT J0800.7−4309 and 1SWXRT J230642.8+550817 are cataclysmic variable binary systems. Finally, we found that IGR J14059−6116 is likely associated with the Fermi source 3FGL J1405.4−6119. In the case of XMMSL1 J030715.5−545536, no XRT counterpart was detected. In all the other cases, optical/infrared spectroscopy is necessary to classify properly each X-ray counterpart and confirm their association with the INTEGRAL/IBIS detection.
Zenker's diverticulum is an acquired sac-like outpouching of the mucosa and submucosa layers located dorsally at the pharyngoesophageal junction through Killian's dehiscence. It is the most common ...type of oesophageal diverticula with a reported prevalence ranging between 0.01 to 0.11% and typically occurs in middle-aged and elderly patients. Predominant symptoms are dysphagia and regurgitation. Treatment is recommended for symptomatic patients and considering the aetiopathogenesis of the disease demands myotomy of the cricopharyngeal muscle. Myotomy may be pursued through either open surgical or endoscopic techniques. Management of Zenker's diverticulum has dramatically progressed during past decades. Open surgery with cricopharyngeal myotomy has long been the conventional treatment with satisfactory results, but is associated with high complication rates. Since Zenker's diverticulum mainly affects frail elderly patients, less invasive treatments are indicated. In recent years, endoscopic repair of Zenker's diverticulum has been found to be a viable safe and effective alternative to surgery and gained widespread acceptance. Endoscopic stapled diverticulotomy is generally the preferred approach, but flexible endoscopy is a valuable option, particularly for high-risk patients. The literature is mainly based on retrospective case series or comparative case series, and the optimal treatment modality has not yet been established. The choice between the different approaches depends on local expertise and preferences. Based on retrospective literature results, appropriate technique selection dictated by the size of the diverticulum and the patient's conditions is however desirable.
Pancreas divisum (PD) is a congenital variant of the pancreatic ductal system and a potential cause of acute recurrent pancreatitis (ARP). Endoscopic minor papilla sphincterotomy (MiES) is the most ...common procedure performed in the management of PD-related ARP. The aim of this study is to perform a meta-analysis estimating the efficacy and the safety of MiES in the management of patients with PD-related ARP.
A research was performed in Pubmed, EMBASE and Web of science, the studies were reviewed and selected according to inclusion and exclusion criteria. Evaluation of Heterogeneity and publication bias was performed, and a random effect model was used to estimate the effect size of each study.
One hundred and thirteen articles were selected and reviewed, 13 met the inclusion criteria. All the studies were retrospective with a mean follow-up duration of 45.9 months. A total of 323 patients with PD-related ARP treated with MiES were included in the meta-analysis. The overall clinical success rate of MiES (defined as no further episodes of ARP, reduction of episodes of ARP, or improvement in quality of life) was of 77% (95%CI: 72%-81%;
= 0.30). Evaluating only the studies with clinical success rate defined as "no further AP in the follow-up" the clinical success rate was of 69.8% (95%CI: 61.3%-77.2%;
= 0.57), while evaluating the studies with other definitions (reduction of episodes of ARP or improvement in quality of life) the clinical success rate was of 81.2% (95%CI: 75.2%-86.1%;
= 0.45). The common fixed effects model disclosed a 25.5% overall adverse events rate (95%CI: 19.3%-32.8%;
= 0.42): acute pancreatitis in 14.3% (95%CI: 9.7%-20.6%;
= 0.36), bleeding in 5.6% (95%CI: 2.9%-10.4%;
= 0.98), and other adverse events in 5.6% (95%CI: 2.9%-10.4%;
= 0.67).
MiES is an effective and relatively safe treatment in the management of PD-related ARP. The retrospective nature of the studies selected is the main limitations of this metanalysis. Prospective trials are needed to confirm these data.
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