D-Fagomine lowers postprandial blood glucose and modulates bacterial adhesion

d-Fagomine is an iminosugar originally isolated from seeds of buckwheat (Fagopyrum sculentum Moench), present in the human diet and now available as a pure crystalline product. We tested d-fagomine for activities connected to a reduction in the risk of developing insulin resistance, becoming overweight and suffering from an excess of potentially pathogenic bacteria. The activities were: intestinal sucrase inhibition in vitro (rat mucosa and everted intestine sleeves), modulation of postprandial blood glucose in rats, bacterial agglutination and bacterial adhesion to pig intestinal mucosa. When ingested together with sucrose or starch, d-fagomine lowered blood glucose in a dose-dependent manner without stimulating insulin secretion. d-Fagomine reduced the area under the curve (0-120 min) by 20 % (P < 0•01) and shifted the time to maximum blood glucose concentration (T max) by 15 min at doses of 1-2 mg/kg body weight when administered together with 1 g sucrose/kg body weight. Moreover, d-fagomine (0•14 mm) agglutinated 60 % of Enterobacteriaceae (Escherichia coli, Salmonella enterica serovar Typhimurium) populations (P < 0•01), while it did not show this effect on Bifidobacterium spp. or Lactobacillus spp. At the same concentration, d-fagomine significantly (P < 0•001) inhibited the adhesion of Enterobacteriaceae (95-99 % cells in the supernatant) and promoted the adhesion of Lactobacillus acidophilus (56 % cells in the supernatant) to intestinal mucosa. d-Fagomine did not show any effect on bacterial cell viability. Based on all this evidence, d-fagomine may be used as a dietary ingredient or functional food component to reduce the health risks associated with an excessive intake of fast-digestible carbohydrates, or an excess of potentially pathogenic bacteria. © 2011 The Authors

Single-locus-sequence-based typing of the mgpB gene reveals transmission dynamics in mycoplasma genitalium

Sexually transmitted infections (STIs) by Mycoplasma genitalium are a major problem worldwide, especially given their marked and rapid propensity for developing antimicrobial resistance. Since very few treatment options exist, clinicians face an important challenge in the management of the infection. In this scenario, little is known regarding the transmission dynamics of M. genitalium and the epidemiology of antimicrobial resistance. This mgpB-based molecular typing study, conducted among 54 asymptomatically infected individuals prospectively recruited from an STI screening service, reveals two distinct epidemiological clusters that significantly correlate with sexual conduct in heterosexuals and men who have sex with men (MSM), respectively. This well-defined structuration suggests the presence of two independent sexual networks with little connectivity between them. On the other hand, the study demonstrates the multiclonal feature of the emergence of antibiotic resistance in M. genitalium to both macrolides and fluoroquinolones. The high prevalence of macrolide resistance in M. genitalium among MSM, influenced by dense network connectivity and strong antibiotic selective pressure, may correspond to allodemics affecting other STIs such as gonorrhea, syphilis and enteric pathogens. Collaterally, the structural and functional impact of mutations in the mgpB gene, encoding the major adhesin P140 (MgpB), may require further investigation.This work was partially supported by an “Ayuda SEIMC” grant from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC)

Transmission of sheep-bovine spongiform encephalopathy in pigs

The transmissible spongiform encephalopathies (TSE) don´t occur in swine in natural conditions. However, the bovine spongiform encephalopathy (BSE) agent, inoculated by 3 simultaneous routes in pigs, is able to reproduce a neurological disease in these animals. On the other hand, the BSE agent after passage in sheep under experimental conditions (sheep-BSE) exhibits altered pathobiologic properties. This new agent is able to cross the cattle-pig transmission barrier more efficiently than BSE..

Standardized Hepatitis B Virus RNA Quantification in Untreated and Treated Chronic Patients: a Promising Marker of Infection Follow-Up.

The measurement and interpretation of HBV DNA and RNA levels in HBV infected patients treated with antiviral therapy supports the objective of HBV disease management. Here, we quantified circulating HBV RNA through a standardized and sensitive assay in follow-up samples from both naive and treated patients as a marker of infection evolution. HBV DNA (HBV DNA for use in Cobas 6800/8800 Automated Roche Molecular Systems), RNA (Roche HBV RNA Investigational Assay for use in the Cobas 6800/8800; Roche), HBeAg and HBsAg (Elycsys HBsAg chemiluminescence immunoassay by Cobas 8000; Roche), and core-related antigen (Lumipulse G chemiluminescence assay; Fujirebio) levels were measured in cohorts of untreated or nucleos(t)ide treated, HBV-infected subjects in an outpatient hospital setting. HBV DNA levels in untreated people were 3.6 log10 higher than corresponding RNA levels and were stable over 5 years of observation. While only five of 52 treated patients had DNA levels below the lower limit of quantification (10 IU/mL) at the end of follow-up, 13 had HBV RNA levels persistently above this limit, including eight with undetectable DNA. In samples with undetectable core-related antigen we observed a median HBsAg titer 2.7-fold higher than in samples with undetectable RNA (adjusted P = 0.012). Detectable HBV RNA with undetectable HBV DNA was a negative predictor of HBsAg decrease to a level ≤100 IU/mL (P = 0.03). In naive patients the difference between HBV DNA and RNA was higher than previously reported. HBV RNA rapidly decreased during treatment. However, in some cases, it was detectable even after years of effective therapy, being a negative predictor of HBsAg decrease. The investigational RNA assay for use on the Cobas 6800/8800 instruments is a sensitive and standardized method that could be applied in general management of HBV infection. IMPORTANCE This study focused on the quantification of circulating HBV RNA by using a standardized and sensitive assay. Thanks to this system we observed a higher difference between circulating HBV DNA and RNA than previously reported. In treated patients, HBV RNA decreased together with DNA, although some patients presented detectable levels even after years of successful antiviral treatment, suggesting a persistent viral transcription. Of note, the detection of viral RNA when HBV DNA is undetectable was a negative predictor of HBsAg decrease to a level ≤100 IU/mL. This assay could be extremely helpful in HBV patients management to study viral transcription and to identify those treated patients that may achieve sustained viral suppression

Synthesizing Coupled 3D Face Modalities by Trunk-Branch Generative Adversarial Networks

Generating realistic 3D faces is of high importance for computer graphics and computer vision applications. Generally, research on 3D face generation revolves around linear statistical models of the facial surface. Nevertheless, these models cannot represent faithfully either the facial texture or the normals of the face, which are very crucial for photo-realistic face synthesis. Recently, it was demonstrated that Generative Adversarial Networks (GANs) can be used for generating high-quality textures of faces. Nevertheless, the generation process either omits the geometry and normals, or independent processes are used to produce 3D shape information. In this paper, we present the first methodology that generates high-quality texture, shape, and normals jointly, which can be used for photo-realistic synthesis. To do so, we propose a novel GAN that can generate data from different modalities while exploiting their correlations. Furthermore, we demonstrate how we can condition the generation on the expression and create faces with various facial expressions. The qualitative results shown in this paper are compressed due to size limitations, full-resolution results and the accompanying video can be found in the supplementary documents. The code and models are available at the project page: https://github.com/barisgecer/TBGAN.Comment: Check project page: https://github.com/barisgecer/TBGAN for the full resolution results and the accompanying vide

The emergence of classical BSE from atypical/Nor98 scrapie

Atypical/Nor98 scrapie (AS) is a prion disease of small ruminants. Currently there are no efficient measures to control this form of prion disease, and, importantly, the zoonotic potential and the risk that AS might represent for other farmed animal species remains largely unknown. In this study, we investigated the capacity of AS to propagate in bovine PrP transgenic mice. Unexpectedly, the transmission of AS isolates originating from 5 different European countries to bovine PrP mice resulted in the propagation of the classical BSE (c-BSE) agent. Detection of prion seeding activity in vitro by protein misfolding cyclic amplification (PMCA) demonstrated that low levels of the c-BSE agent were present in the original AS isolates. C-BSE prion seeding activity was also detected in brain tissue of ovine PrP mice inoculated with limiting dilutions (endpoint titration) of ovine AS isolates. These results are consistent with the emergence and replication of c-BSE prions during the in vivo propagation of AS isolates in the natural host. These data also indicate that c-BSE prions, a known zonotic agent in humans, can emerge as a dominant prion strain during passage of AS between different species. These findings provide an unprecedented insight into the evolution of mammalian prion strain properties triggered by intra- and interspecies passage. From a public health perspective, the presence of c-BSE in AS isolates suggest that cattle exposure to small ruminant tissues and products could lead to new occurrences of c-BSE

Hepatitis B Virus Variants with Multiple Insertions and/or Deletions in the X Open Reading Frame 3 ' End: Common Members of Viral Quasispecies in Chronic Hepatitis B Patients

Hepatitis B virus; Insertions; Next-generation sequencingVirus de l'hepatitis B; Insercions; Seqüenciació de nova generacióVirus de la hepatitis B; Inserciones; Secuenciación de próxima generaciónDeletions in the 3′ end region of the hepatitis B virus (HBV) X open reading frame (HBX) may affect the core promoter (Cp) and have been frequently associated with hepatocellular carcinoma (HCC). The aim of this study was to investigate the presence of variants with deletions and/or insertions (Indels) in this region in the quasispecies of 50 chronic hepatitis B (CHB) patients without HCC. We identified 103 different Indels in 47 (94%) patients, in a median of 3.4% of their reads (IQR, 1.3–8.4%), and 25% (IQR, 13.1–40.7%) of unique sequences identified in each quasispecies (haplotypes). Of those Indels, 101 (98.1%) caused 44 different altered stop codons, the most commonly observed were at positions 128, 129, 135, and 362 (putative position). Moreover, 39 (37.9%) Indels altered the TATA-like box (TA) sequences of Cp; the most commonly observed caused TA2 + TA3 fusion, creating a new putative canonical TATA box. Four (8%) patients developed negative clinical outcomes after a median follow-up of 9.4 (8.7–12) years. In conclusion, we observed variants with Indels in the HBX 3′ end in the vast majority of our CHB patients, some of them encoding alternative versions of HBx with potential functional roles, and/or alterations in the regulation of transcription.This research was funded by Instituto de Salud Carlos III and co-financed by the European Regional Development Fund (ERDF), grant number PI18/01436; PI19/00301; and by the Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant number IDI-20200297. The APC was funded by the grant PI18/01436

International Veterinary Epilepsy Task Force Consensus Proposal: Diagnostic approach to epilepsy in dogs

This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset 6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose

Anti-tumour immune response in GL261 glioblastoma generated by Temozolamide Immune-Enhancing Metronomic Schedule monitored with MRSI-based nosological images

Glioblastomas (GB) are brain tumours with poor prognosis even after aggressive therapy. Improvements in both therapeutic and follow-up strategies are urgently needed. In previous work we described an oscillatory pattern of response to Temozolomide (TMZ) using a standard administration protocol, detected through MRSI-based machine learning approaches. In the present work, we have introduced the Immune-Enhancing Metronomic Schedule (IMS) with an every 6-days TMZ administration at 60mg/kg, and investigated the consistence of such oscillatory behaviour. A total of n=17 GL261 GB tumour-bearing C57BL/6j mice were studied with MRI/MRSI every 2 days, and the oscillatory behaviour (6.2±1.5 days period from the TMZ administration day) was confirmed during response. Furthermore, IMS-TMZ produced significant improvement in mice survival (22.5±3.0 days for controls vs 135.8±78.2 for TMZ-treated), outperforming standard TMZ treatment. Histopathological correlation was investigated in selected tumour samples (n=6) analyzing control and responding fields. Significant differences were found for CD3+ cells (lymphocytes, 3.3±2.5 vs 4.8±2.9 respectively) and Iba-1 immunostained area (microglia/macrophages, 16.8±9.7% and 21.9±11.4% respectively). Unexpectedly, during IMS-TMZ treatment, tumours from some mice (n=6) fully regressed and remained undetectable without further treatment for one month. These animals were considered “cured” and a GL261 re-challenge experiment performed, with no tumour reappearance in 5 out of 6 cases. Heterogeneous therapy response outcomes were detected in tumour-bearing mice, and a selected group was investigated (n=3 non-responders, n=6 relapsing tumours, n=3 controls). PD-L1 content was found ca. 3-fold increased in the relapsing group when comparing with control and non-responding groups, suggesting that increased lymphocyte inhibition could be associated to IMS-TMZ failure. Overall, data suggest that host immune response has a relevant paper in therapy response/escape in GL261 tumours under IMS-TMZ therapy. This is associated to changes in the metabolomics pattern, oscillating every 6 days, in agreement with immune cycle length, which is being sampled by MRSI-derived nosological images

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations