Impairment of muscular endothelial cell regeneration in dermatomyositis.

Background and aim: Inflammatory myopathies are heterogeneous in terms of etiology, (immuno)pathology, and clinical findings. Endothelial cell injury, as it occurs in DM, is a common feature of numerous inflammatory and non-inflammatory vascular diseases. Vascular regeneration is mediated by both local and blood-derived mechanisms, such as the mobilization and activation of so-called proangiogenic cells (PACs) or early endothelial progenitor cells (eEPCs). The current study aimed to evaluate parameters of eEPC integrity in dermatomyositis (DM), compared to necrotizing myopathy (NM) and to non-myopathic controls. Methods: Blood samples from DM and NM patients were compared to non-myositis controls and analyzed for the following parameters: circulating CD133+/VEGFR-2+ cells, number of colony-forming unit endothelial cells (CFU-ECs), concentrations of angiopoietin 1, vascular endothelial growth factor (VEGF), and CXCL-16. Muscle biopsies from DM and NM subjects underwent immunofluorescence analysis for CXCR6, nestin, and CD31 (PECAM-1). Finally, myotubes, derived from healthy donors, were stimulated with serum samples from DM and NM patients, subsequently followed by RT-PCR for the following candidates: IL-1ß, IL-6, nestin, and CD31. Results: Seventeen (17) DM patients, 7 NM patients, and 40 non-myositis controls were included. CD133+/VEGFR-2+ cells did not differ between the groups. Both DM and NM patients showed lower CFU-ECs than controls. In DM, intramuscular CD31 abundances were significantly reduced, which indicated vascular rarefaction. Muscular CXCR6 was elevated in both diseases. Circulating CXCL-16 was higher in DM and NM in contrast, compared to controls. Serum from patients with DM but not NM induced a profound upregulation of mRNS expression of CD31 and IL-6 in cultured myotubes. Conclusion: Our study demonstrates the loss of intramuscular microvessels in DM, accompanied by endothelial activation in DM and NM. Vascular regeneration was impaired in DM and NM. The findings suggest a role for inflammation-associated vascular damage in the pathogenesis of DM.

[Colchicine and non-severe ocular inflammation excluding Behcet's disease: 16 cases and literature review]. / Colchicine et inflammation oculaire non sévère hors maladie de Behcet : 16 cas et revue de la littérature.

INTRODUCTION: Colchicine is a narrow therapeutic margin drug that does not have the adverse effects of corticosteroids and immunosuppressants. Its use in non-severe ocular inflammatory disease excluding Behcet's disease has not been studied. METHODS: We included patients seen in the internal medicine department of Dijon University Hospital consecutively between September 2020 and September 2021 if they had received colchicine during their pathology. Patients with suspected Behçet's disease were excluded. Treatment efficacy was studied in patients with at least one year of disease progression who had received more than one year of colchicine. Successful treatment was defined as a 50 % reduction in the number of annual relapses on colchicine. RESULTS: Sixteen patients were included (9 women and 7 men). They had recurrent anterior uveitis (n=10), recurrent scleritis (n=5) and intermediate uveitis. Opthalmological involvement was neither severe nor complicated. All patients combined, the annual relapse ratio (ARR) decreased from 1.8 (0.8-3.5) to 0.3 (0-1.6), (P=0.06). Colchicine was considered effective in three of 10 analyzable patients. In only one patient, treatment was stopped for adverse effects after six weeks. CONCLUSION: In view of the interesting benefit-risk ratio of colchicine, it seems appropriate to focus on this molecule in non-granulomatous anterior uveitis and non-severe recurrent scleritis.

Predictive preoperative clinical score for patients with liver-only oligometastatic colorectal cancer.

BACKGROUND: Resection of liver metastases from colorectal cancer (CRC) in the oligometastatic stage improves survival and is a potentially curative treatment. Thus, predictive scores that reliably identify those patients who especially benefit from surgery are essential. PATIENTS AND METHODS: In this multicenter analysis, 512 patients had undergone surgery for liver metastases from CRC. We investigated distinct cancer-specific risk factors that are routinely available in clinical practice and developed a predictive preoperative score using a training cohort (TC), which was thereafter tested in a validation cohort (VC). RESULTS: Inflammatory response to the tumor, a right-sided primary tumor, multiple liver metastases, and node-positive primary tumor were significant adverse variables for overall survival (OS). Patients were stratified in five groups according to the cumulative score given by the presence of these risk factors. Median OS for patients without risk factors was 133.8 months [95% confidence interval (CI) 81.2-not reached (nr)] in the TC and was not reached in the VC. OS decreased significantly for each subsequent group with increasing number of risk factors. Median OS was significantly shorter (P < 0.0001) for patients presenting all four risk factors: 14.3 months (95% CI 10.5 months-nr) in the TC and 16.6 months (95% CI 14.6 months-nr) in the VC. CONCLUSIONS: Including easily obtainable variables, this preoperative score identifies oligometastatic CRC patients with prolonged survival rates that may be cured, and harbors potential to be implemented in daily clinical practice.

Ischemic injury of the upper gastrointestinal tract after out-of-hospital cardiac arrest: a prospective, multicenter study.

BACKGROUND: The consequences of cardiac arrest (CA) on the gastro-intestinal tract are poorly understood. We measured the incidence of ischemic injury in the upper gastro-intestinal tract after Out-of-hospital CA (OHCA) and determined the risk factors for and consequences of gastrointestinal ischemic injury according to its severity. METHODS: Prospective, non-controlled, multicenter study in nine ICUs in France and Belgium conducted from November 1, 2014 to November 30, 2018. Included patients underwent an esophago-gastro-duodenoscopy 2 to 4 d after OHCA if still intubated and the presence of ischemic lesions of the upper gastro-intestinal tract was determined by a gastroenterologist. Lesions were a priori defined as severe if there was ulceration or necrosis and moderate if there was mucosal edema or erythema. We compared clinical and cardiac arrest characteristics of three groups of patients (no, moderate, and severe lesions) and identified variables associated with gastrointestinal ischemic injury using multivariate regression analysis. We also compared the outcomes (organ failure during ICU stay and neurological status at hospital discharge) of the three groups of patients. RESULTS: Among the 214 patients included in the analysis, 121 (57%, 95% CI 50-63%) had an upper gastrointestinal ischemic lesion, most frequently on the fundus. Ischemic lesions were severe in 55/121 (45%) patients. In multivariate regression, higher adrenaline dose during cardiopulmonary resuscitation (OR 1.25 per mg (1.08-1.46)) was independently associated with increased odds of severe upper gastrointestinal ischemic lesions; previous proton pump inhibitor use (OR 0.40 (0.14-1.00)) and serum bicarbonate on day 1 (OR 0.89 (0.81-0.97)) were associated with lower odds of ischemic lesions. Patients with severe lesions had a higher SOFA score during the ICU stay and worse neurological outcome at hospital discharge. CONCLUSIONS: More than half of the patients successfully resuscitated from OHCA had upper gastrointestinal tract ischemic injury. Presence of ischemic lesions was independently associated with the amount of adrenaline used during resuscitation. Patients with severe lesions had higher organ failure scores during the ICU stay and a worse prognosis. Clinical Trial Registration NCT02349074 .

Potentials and current shortcomings in the cooperation between German centers for rare diseases and primary care physicians: results from the project TRANSLATE-NAMSE.

BACKGROUND: The TRANSLATE-NAMSE project with the strengthening of the centers for rare diseases with their affiliation to the European Reference Networks was a major step towards the implementation of the German National Plan of Action for People with Rare Diseases establishing better care structures. As primary care physicians, general practitioners and pediatricians play a central role in the diagnosis of patients with rare disease, as it is usually them referring to specialists and rare disease centers. Therefore, the interface management between primary care physicians and the centers for rare diseases is of particular importance. METHODS: In a mixed-method-approach an anonymous postal survey of 1,500 randomly selected primary care physicians in Germany was conducted with focus on (1) knowledge about a center for rare diseases and how it works, (2) in case of cooperation, satisfaction with the services provided by centers, and (3) expectations and needs they have with regard to the centers. In addition, in-depth telephone interviews were conducted with physicians who had already referred patients to a center. RESULTS: In total, 248 physicians responded to the survey, and 15 primary care physicians were interviewed. We observed a wide lack of knowledge about the existence of (45.6% confirmed to know at least one center) about how to access rare disease centers (50.4% of those who know a center confirmed knowledge) and what the center specializes in. In case of cooperation the evaluation was mostly positive. CONCLUSION: To improve medical care, the interplay between primary care physicians and rare disease centers needs to be strengthened. (1) To improve the communication, the objectives and functioning of the rare disease centers should become more visible. (2) Other projects dealing with the analysis and improvement of interface management between centers and primary care physicians, as described in the National Plan of Action for People with Rare Diseases, need to be implemented immediately. (3) If the project is evaluated positively, the structures of TRANSLATE-NAMSE should be introduced nationwide into the German health care system to ensure comprehensive, quality-assured care for people with rare diseases with special consideration of the key role of primary care physicians-also taking into account the financial expenditures of this new care model.

Adaptive Control Improves Sclera Force Safety in Robot-Assisted Eye Surgery: A Clinical Study.

The integration of robotics into retinal microsurgery leads to a reduction in surgeon perception of tool-to-tissue interaction forces. This blunting of human tactile sensory input, which is due to the inflexible mass and large inertia of the robotic arm as compared to the milli-Newton scale of the interaction forces and fragile tissues during ophthalmic surgery, identifies a potential iatrogenic risk during robotic eye surgery. In this paper, we aim to evaluate two variants of an adaptive force control scheme implemented on the Steady-Hand Eye Robot (SHER) that are intended to mitigate the risk of unsafe scleral forces. The present study enrolled ten retina fellows and ophthalmology residents into a simulated procedure, which simply asked the trainees to follow retinal vessels in a model retina surgery environment. For this purpose, we have developed a force-sensing (equipped with Fiber Bragg Grating (FBG)) instrument to attach to the robot. A piezo-actuated linear stage for creating random lateral motions to the eyeball phantom has been provided to simulate disturbances during surgery. The SHER and all of its dependencies were set up in an operating room in the Wilmer Eye Institute at the Johns Hopkins Hospital. The clinicians conducted robot-assisted experiments with the adaptive controls incorporated as well as freehand manipulations. The results indicate that the Adaptive Norm Control (ANC) method, is able to maintain scleral forces at predetermined safe levels better than even freehand manipulations. Novice clinicians in robot training however, subjectively preferred freehand maneuvers over robotic manipulations. Clinician preferences once highly skilled with the robot is not assessed in this study.

PAC-Mediated AKI Protection Is Critically Mediated but Does Not Exclusively Depend on Cell-Derived Microvesicles.

INTRODUCTION: Acute kidney injury (AKI) significantly worsens the prognosis of hospitalized patients. In recent years, cell-based strategies have been established as a reliable option for improving AKI outcomes in experimental AKI. Our previous studies focused on the so-called proangiogenic cells (PACs). Mechanisms that contribute to PAC-mediated AKI protection include production/secretion of extracellular vesicles (MV, microvesicles). In addition, the cells most likely act by paracrinic processes (secretome). The current study evaluated whether AKI may be preventable by the administration of either PAC-derived MV and/or the secretome alone. METHODS: AKI was induced in male C57/Bl6N mice (8-12 weeks) by bilateral renal ischemia (IRI-40 minutes). Syngeneic murine PACs were stimulated with either melatonin, angiopoietin-1 or -2, or with bone morphogenetic protein-5 (BMP-5) for one hour, respectively. PAC-derived MV and the vesicle-depleted supernatant were subsequently collected and i.v.-injected after ischemia. Mice were analyzed 48 hours later. RESULTS: IRI induced significant kidney excretory dysfunction as reflected by higher serum cystatin C levels. The only measure that improved AKI was the injection of MV, collected from native PACs. The following conditions worsened after ischemic renal function even further: MV + Ang-1, MV + BMP-5, MV + melatonin, and MV + secretome + Ang-1. CONCLUSION: Together, our data show that PAC-mediated AKI protection substantially depends on the availability of cell-derived MV. However, since previous data showed improved AKI-protection by PACs after cell preconditioning with certain mediators (Ang-1 and -2, melatonin, BMP-5), mechanisms other than exclusively vesicle-dependent mechanisms must be involved in PAC-mediated AKI protection.

Analysis of the lipid extraction performance in a cascade process for Scenedesmus almeriensis biorefinery.

BACKGROUND: Microalgae have attracted considerable interest due to their ability to produce a wide range of valuable compounds. Pulsed Electric Fields (PEF) has been demonstrated to effectively disrupt the microalgae cells and facilitate intracellular extraction. To increase the commercial viability of microalgae, the entire biomass should be exploited with different products extracted and valorized according to the biorefinery scheme. However, demonstrations of multiple component extraction in series are very limited in literature. This study aimed to develop an effective lipid extraction protocol from wet Scenedesmus almeriensis after PEF-treatment with 1.5 MJ·kgDW-1. A cascade process, i.e., the valorization of several products in row, was tested with firstly the collection of the released carbohydrates in the water fraction, then protein enzymatic hydrolysis and finally lipid extraction. Biomass processed with high pressure homogenization (HPH) on parallel, served as benchmark. RESULTS: Lipid extraction with ethanol:hexane (1:0.41 vol/vol) offered the highest yields from the different protocols tested. PEF-treatment promoted extraction with almost 70% of total lipids extracted against 43% from untreated biomass. An incubation step after PEF-treatment, further improved the yields, up to 83% of total lipids. Increasing the solvent volume by factor 2 offered no improvement. In comparison, extraction with two other systems utilizing only ethanol at room temperature or elevated at 60 °C were ineffective with less than 30% of total lipids extracted. Regarding cascade extraction, carbohydrate release after PEF was detected albeit in low concentrations. PEF-treated samples displayed slightly better kinetics during the enzymatic protein hydrolysis compared to untreated or HPH-treated biomass. The yields from a subsequent lipid extraction were not affected after PEF but were significantly increased for untreated samples (66% of total lipids), while HPH displayed the lowest yields (~ 49% of total lipids). CONCLUSIONS: PEF-treatment successfully promoted lipid extraction from S. almeriensis but only in combination with a polar:neutral co-solvent (ethanol:hexane). After enzymatic protein hydrolysis in cascade processing; however, untreated biomass displayed equal lipid yields due to the disruptive effect of the proteolytic enzymes. Therefore, the positive impact of PEF in this scheme is limited on the improved reaction kinetics exhibited during the enzymatic hydrolysis step.

Deep Learning Detection of Sea Fan Neovascularization From Ultra-Widefield Color Fundus Photographs of Patients With Sickle Cell Hemoglobinopathy.

Importance: Adherence to screening for vision-threatening proliferative sickle cell retinopathy is limited among patients with sickle cell hemoglobinopathy despite guidelines recommending dilated fundus examinations beginning in childhood. An automated algorithm for detecting sea fan neovascularization from ultra-widefield color fundus photographs could expand access to rapid retinal evaluations to identify patients at risk of vision loss from proliferative sickle cell retinopathy. Objective: To develop a deep learning system for detecting sea fan neovascularization from ultra-widefield color fundus photographs from patients with sickle cell hemoglobinopathy. Design, Setting, and Participants: In a cross-sectional study conducted at a single-institution, tertiary academic referral center, deidentified, retrospectively collected, ultra-widefield color fundus photographs from 190 adults with sickle cell hemoglobinopathy were independently graded by 2 masked retinal specialists for presence or absence of sea fan neovascularization. A third masked retinal specialist regraded images with discordant or indeterminate grades. Consensus retinal specialist reference standard grades were used to train a convolutional neural network to classify images for presence or absence of sea fan neovascularization. Participants included nondiabetic adults with sickle cell hemoglobinopathy receiving care from a Wilmer Eye Institute retinal specialist; the patients had received no previous laser or surgical treatment for sickle cell retinopathy and underwent imaging with ultra-widefield color fundus photographs between January 1, 2012, and January 30, 2019. Interventions: Deidentified ultra-widefield color fundus photographs were retrospectively collected. Main Outcomes and Measures: Sensitivity, specificity, and area under the receiver operating characteristic curve of the convolutional neural network for sea fan detection. Results: A total of 1182 images from 190 patients were included. Of the 190 patients, 101 were women (53.2%), and the mean (SD) age at baseline was 36.2 (12.3) years; 119 patients (62.6%) had hemoglobin SS disease and 46 (24.2%) had hemoglobin SC disease. One hundred seventy-nine patients (94.2%) were of Black or African descent. Images with sea fan neovascularization were obtained in 57 patients (30.0%). The convolutional neural network had an area under the curve of 0.988 (95% CI, 0.969-0.999), with sensitivity of 97.4% (95% CI, 86.5%-99.9%) and specificity of 97.0% (95% CI, 93.5%-98.9%) for detecting sea fan neovascularization from ultra-widefield color fundus photographs. Conclusions and Relevance: This study reports an automated system with high sensitivity and specificity for detecting sea fan neovascularization from ultra-widefield color fundus photographs from patients with sickle cell hemoglobinopathy, with potential applications for improving screening for vision-threatening proliferative sickle cell retinopathy.

Light Modulates Important Pathogenic Determinants and Virulence in ESKAPE Pathogens Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus.

Light sensing has been extensively characterized in the human pathogen Acinetobacter baumannii at environmental temperatures. However, the influence of light on the physiology and pathogenicity of human bacterial pathogens at temperatures found in warm-blooded hosts is still poorly understand. In this work, we show that Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa (ESKAPE) priority pathogens, which have been recognized by the WHO and the CDC as critical, can also sense and respond to light at temperatures found in human hosts. Most interestingly, in these pathogens, light modulates important pathogenicity determinants as well as virulence in an epithelial infection model, which could have implications in human infections. In fact, we found that alpha-toxin-dependent hemolysis, motility, and growth under iron-deprived conditions are modulated by light in S. aureus Light also regulates persistence, metabolism, and the ability to kill competitors in some of these microorganisms. Finally, light exerts a profound effect on the virulence of these pathogens in an epithelial infection model, although the response is not the same in the different species; virulence was enhanced by light in A. baumannii and S. aureus, while in A. nosocomialis and P. aeruginosa it was reduced. Neither the BlsA photoreceptor nor the type VI secretion system (T6SS) is involved in virulence modulation by light in A. baumannii Overall, this fundamental knowledge highlights the potential use of light to control pathogen virulence, either directly or by manipulating the light regulatory switch toward the lowest virulence/persistence configuration.IMPORTANCE Pathogenic bacteria are microorganisms capable of producing disease. Dangerous bacterial pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, are responsible for serious intrahospital and community infections in humans. Therapeutics is often complicated due to resistance to multiple antibiotics, rendering them ineffective. In this work, we show that these pathogens sense natural light and respond to it by modulating aspects related to their ability to cause disease; in the presence of light, some of them become more aggressive, while others show an opposite response. Overall, we provide new understanding on the behavior of these pathogens, which could contribute to the control of infections caused by them. Since the response is distributed in diverse pathogens, this notion could prove a general concept.

Boomslang (Dispholidus typus) envenomation in a patient on warfarin therapy.

The venom of the boomslang (Dispholidus typus) has potent effects on the coagulation system. It is known to produce a venom-induced consumptive coagulopathy (VICC) through the proposed activation of clotting factor II (prothrombin), factor X, and possibly factor IX. Warfarin, an anticoagulant medication, decreases the circulating vitamin K-dependent clotting factors II, VII, IX and X. We report a unique case of a boomslang bite in a patient on warfarin therapy. During the patient's hospital stay he developed abnormal clotting profiles indicating an underlying VICC, but without major bleeding. He received monovalent antivenom and recovered with no complications. We discuss two possible outcomes of a boomslang bite in a patient on warfarin therapy, exploring the underlying pathophysiology that could lead to the presentation of a reduced risk of overall bleeding or, alternatively, that the bleeding could be compounded and exacerbated. It is possible that in our case the anticoagulant effect of warfarin was wholly obscured by the VICC of the boomslang venom. The composition of the snake venom may have been a contributory factor in the reduced clinical bleeding observed.

Robotic Retinal Surgery Impacts on Scleral Forces: In Vivo Study.

Purpose: This study aims to map force interaction between instrument and sclera of in vivo rabbits during retinal procedures, and verify if a robotic active force control could prevent unwanted increase of forces on the sclera. Methods: Experiments consisted in the performance of intraocular movements of a force sensing instrument, adjacent to the retinal surface, in radial directions, from the center to the periphery and back, and compared manual manipulations with robotic assistance and also robotic assistance with an active force control. This protocol was approved by the Animal Use and Ethical Committee and experiments were according to ARVO Statement of Animal Use. Results: Mean forces using manual manipulations were 115 ± 51 mN. Using robotic assistance, mean forces were 118 ± 49 mN. Using an active force control method, overall mean forces reduced to 69 ± 15, with a statistical difference compared with other methods (P < 0.001). Comparing intraocular directions, superior sector required higher forces and the force control method reduced differences in forces between users and retained the same force pattern between them. Conclusions: Results validate that the introduction of robotic assistance might increase the dynamic interactions between instrument and sclera, and the addition of an active force control method reduces the forces at levels lower than manual manipulations. Translational Relevance: All marketing benefits from extreme accuracy and stability from robots, however, redundancy of safety mechanisms during intraocular manipulations, especially on force control and surgical awareness, would allow all utility of robotic assistance in ophthalmology.

Advanced field emission measurement techniques for research on modern cold cathode materials and their applications for transmission-type x-ray sources.

We report on the functional capabilities of our field emission (FE) measurement systems. The samples are prepared and inserted under clean room conditions and can be precisely xyz-positioned, heat-treated, and investigated in different vacuum environments and temperatures. The FE scanning microscope is a unique microscope being used for the localization of FE sites with high lateral resolution by means of extraction voltage U(x, y) or emission current I(x, y) maps over the cathode area of 25 × 25 mm2 and measuring the FE properties of localized emission sites or individual emitters. In contrast, the integral measurement system with the luminescent screen provides real-time integral information about the distribution of emission sites over the whole cathode during long- and short-term current stability measurements, thus allowing us to investigate the properties of various materials and their applications. Commissioning results with the upgraded systems using a silicon emitter array and a point-type graphene emitter will be given to demonstrate that both FE measurement techniques are very useful for an improved understanding and tailoring of materials for applications. The results showed that point-type graphene emitters are more preferable for practical applications. Using simulation software, a suitable triode configuration for point emitters was designed, and a current transmission ratio of ∼100% was obtained. The FE current stability of graphene emitters at pressures >10-3 Pa can be improved by heating the cathode at 100 °C-300 °C for 1 min-30 min. Finally, point-type graphene film emitters were used for transmission-type x-ray sources, and their applications in imaging and fluorescence spectroscopy are presented.

[The Respiratory Syncytial Virus (RSV) in Adults]. / Das Respiratorische Synzytial-Virus beim Erwachsenen.

RSV induces an acute viral disease with involvement of the respiratory tract. It can be notably life-threatening for infants but also for older adults. New RSV-subtypes are constantly evolving globally. The knowledge about epidemiology, hygiene measures, diagnostics and clinical feature is essential not only for the paediatrician. Vaccines or specific therapeutics are still missing. This article gives an overview with focus on RSV in adults. In addition, molecular pathological characteristics of the virus are explained, research approaches concerning vaccines and therapeutics are mentioned and current problems in management are discussed.

Predictive models of minimum temperatures for the south of Buenos Aires province.

Depending on the time of development of a crop temperature below 0 °C can cause damage to the plant, altering its development and subsequent yield. Since frosts are identified from the minimum air temperature, the objective of this research paper is to generate forecast -(predictive) models at 1, 3 and 5 days of the minimum daily temperature (Tmin) for Bahía Blanca city. Non-linear numerical models are generated using artificial neural networks and geometric models of finite elements. Six independent variables are used: temperature and dew point temperature at meteorological shelter level, relative humidity, cloudiness observed above the station, wind speed and direction measured at 10 m altitude. Data have been obtained between May and September from 1956 to 2015. Once the available data had been analyzed, this period was reduced to 2007-2015. For the selection of the most suitable model, the correlation coefficient of Pearson (R), the determination coefficient (R2) and the Mean Absolute Error (MAE) are evaluated. The results of the study determine that the geometric model of finite elements with 4 variables, over 9 years (2007-2015) and separated by the season of the year is the one that presents better adjustment in the forecast of Tmin with up to 5 days of anticipation.

Gastrointestinal helminths of wolves (Canis lupus Linnaeus, 1758) in Piedmont, north-western Italy.

Free-ranging grey wolves (Canis lupus), which are presently recolonizing Italy, can be parasitized by a diversity of helminths, but have rarely been subject to studies of their parasites. Therefore, this study aims to determine the prevalence of gastrointestinal helminths of road-killed grey wolves from the Piedmont region of Italy. Forty-two wolves were collected and examined for the presence of helminths. We recorded 12 helminth species: nine Nematoda and three Cestoda. The nematodes were: Ancylostoma caninum (7.1%), Capillaria sp. (2.4%), Molineus sp. (2.4%), Pterygodermatites affinis (11.9%), Physaloptera sibirica (9.5%), Toxocara canis (9.5%), Toxascaris leonina (2.4%) and Uncinaria stenocephala (26.2%); the cestodes were: Dipylidium caninum (4.8%), Mesocestoides sp. (4.8%) and Taenia multiceps (76.2%). Physaloptera sibirica had the highest mean intensity and T. multiceps had the highest prevalence. Based on age and sex, no differences in the intensity or prevalence of helminth species were found among the hosts. Molineus sp. was recorded for the first time in wolves from the Palearctic region; P. affinis and P. sibirica are respectively reported for the first time in wolves from Europe and Italy.

Analysis of Direct Effects of the CB1 Receptor Antagonist Rimonabant on Fatty Acid Oxidation and Glycogenolysis in Liver and Muscle Cells in vitro.

Recent pharmacological findings regarding rimonabant, an anorectic and cannabinoid type 1 receptor (CB1R) antagonist, strongly suggest that some of its effects on the metabolic parameters and energy balance in rats are not related to the centrally mediated reduction in caloric intake. Instead, they may be associated with acute induction of glycogenolysis in the liver, in combination with transient increase in glucose oxidation and persistent increase in fat oxidation. It is possible that rimonabant produced direct short- or long-term stimulatory effect on these processes in primary and cultured rat cells. Rimonabant slightly stimulated ß-oxidation of long-chain fatty acids in cultured rat myocytes overexpressing glucose transporter isoform 4, as well as activated phosphorylation of adenosine monophosphate-dependent protein kinase (AMPK) in primary rat hepatocytes upon long-term incubation. However, short-term action of rimonabant failed to stimulate ß-oxidation in myocytes, myotubes, and hepatocytes, as well as to upregulate AMPK phosphorylation, glycogenolysis, and cAMP levels in hepatocytes. As a consequence, the acute effects of rimonabant on hepatic glycogen content (reduction) and total energy expenditure (increase) in rats fed with a standard diet cannot be explained by direct stimulation of glycogenolysis and fatty acid oxidation in muscles and liver. Rather, these effects seem to be centrally mediated.

[Use of biotherapy in the management of Behçet's disease in a department of internal medicine]. / Recours à la biothérapie dans la prise en charge de la maladie de Behçet dans un service de médecine interne.

BACKGROUND: Behçet's disease (BD) is a recurrent multisystemic disease responsible for occlusive vasculitis with arterial, venous and capillary involvement. The aim of this study was to determine the frequency and the features associated with the use of biotherapy in the management of patients followed in our department for BD. METHODS: This is a retrospective study of patients medical records followed for BD in a department of internal medicine from January 2005 to August 2018. RESULTS: A total of 41 patients were included with a mean age at diagnosis of 42.5±12.1 years (range 16 to 63) and a sex ratio men/women of 1.05. Oral and/or genital aphtosis was present in 70.7% of the patients. Other lesions were: ocular (78.0%), articular (46.3%), cutaneous (41.5%), central neurological (34.1%), vascular (26.8%), digestive (7.3%), pericardial (2.4%) and epididymal (2.4%). A biotherapy, interferon α and monoclonal antibodies, was used in 15 patients (36.6%), after failure of conventional treatments. The monoclonal antibodies were anti-TNFα (infliximab, adalimumab, certolizumab and golimumab) except in one patient for whom ustekinumab was used. Biotherapy was used in 46.9% of the patients with ocular involvement and never used in those patients without ocular involvement (P=0.01). CONCLUSION: Biotherapy is effective and represents a solution to the failures of conventional treatments in severe forms of Behçet's disease with ocular involvement.