Investigating on Besnoitia besnoiti (Apicomplexa, Sarcocystidae) in naturally infected dairy cattle by an integrated approach.

Bovine besnoitiosis, caused by Besnoitia besnoiti, is a (re)emerging disease in Europe (Cortes et al., 2014), including Italy (Gazzonis et al., 2014; 2017). However, its economic impact is scarcely considered and generally underestimated and there are still little studied aspects concerning both the parasite and the disease. Following a natural outbreak of besnoitiosis in a dairy herd, a study was planned to characterize B. besnoiti infection in cattle through a multidisciplinary approach.Suspicious abortions and clinical cases of besnoitiosis were reported in a dairy farm (September 2017, Northern Italy) housing 216 Holstein cattle. Blood samples were collected; haematological and serological analyses (ELISA and confirmatory WB) were performed (Fernandez-Garcia et al., 2009). Histology and molecular (endpoint ITS-1 PCR (Cortes et al., 2007) and sequencing) analyses of tissues from a slaughtered cow with chronic besnoitiosis were carried out. Out of 59 ELISA-positive animals, 50 (23%) were confirmed by WB. B. besnoiti prevalence was higher in cows (41%) than in calves (12%); any heifer did not result positive. Considering haematological parameters, a significant shift in the differential leucocyte formula from lymphocyte to granulocyte was recorded in infected cows (Mean±S.D.:L=46.1±18.4,G=53.9±18.4) if compared to negative animals (Student’s T-test,p=0.012). This finding could be helpful in diagnosis, treatment and control of besnoitiosis. Histology revealed a high load of B. besnoiti tissue cysts in skin, vulva, muzzle, sclera, eyelid, respiratory tract, emphasizing the possibility of parasite transmission through direct contact among animals. B. besnoiti was confirmed by PCR in other organs (heart, liver, aorta wall, tonsil) and especially in ovary, uterus and vulva, suggesting that the infection could affect cows’ fertility. Parasite DNA was also found in masseters posing an important question for food security, even if B. besnoiti is not considered zoonotic. The study suggests that to investigate the dynamics of bovine besnoitiosis is mandatory associate clinical and laboratory tests, including the genetic characterization of the parasite and its eventual correlation with the disease outcome

CT of the acute colonic diverticulitis: a pictorial essay

Acute colonic diverticulitis (ACD) is an acute episode of severe and prolonged lower abdominal pain due to diverticular inflammation, usually associated with change in bowel movements, fever, and leukocytosis. Worldwide, computed tomography (CT) of the abdomen and pelvis with intravenous contrast is accepted as the best imaging method for evaluating the diverticular inflammation, serving the following functions: confirming the presence of ACD; evaluation of the disease severity and degree; therapy planning guide in presence of complications (such as abscess or intestinal perforation); diagnosis of other diseases that may simulate diverticular inflammation. In the literature, we found values of CT sensitivity for diverticular inflammation from 79% to 99%; CT is useful in differentiating other diseases, which may cause abdominal pain, when diverticular inflammation is not the cause, such as neoplasm, inflammatory bowel disease, appendix inflammations, epiploic appendix inflammation and colon ischemia. The trick to differentiate diverticulitis from other inflammatory diseases that involve the colon is the identification of diverticula in the pathological intestinal loop. In the last years, a radiological classification was created in order to guide the management of ACD in patients treated conservatively or with interventional procedures. The new classification system divides ACD into two groups: complicated and uncomplicated. Uncomplicated ACD is defined if only thickening of the intestinal wall is present, with increase of the perivisceral fat density. Complicated ACD is divided into 4 stages, depending on presence of microperforation without abscess and/or peritoneum involvement (stage 1 A), presence of abscess with diameter ≤4 cm (stage 1 B), presence of abscess with diameter >4 cm (stage 2 A), presence of distant air >5 cm from the pathological loop (stage 2 B), presence of diffuse fluid in at least two distant abdominal quadrants without distant free air (stage 3), presence of diffuse fluid and distant free air (stage 4). In this pictorial essay, we describe CT findings of the ACD and explain classification of the disease and its common and uncommon complications

Maternal and Sex Dependency of Insulin Resistance: Longitudinal PET and Echocardiography Study from the Healthy Fetus to the Adult Minipig

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Apolipoprotein E polymorphism modulation of asymmetric dimethylarginine in hypertensive patients is determined by renal function

Background: Endothelial dysfunction is considered an early step of atherosclerotic vascular disease. Asymmetric dimethylarginine (ADMA), the main endogenous inhibitor of nitric oxide synthase (NOS), plays a critical role in the process of atherosclerosis in a uremic environment. Increased plasma ADMA not only works as a cardiovascular morbidity biomarker but it is also involved in the genesis of atherosclerosis in renal disease. Considering the relationships of apolipoprotein E(ApoE) polymorphism with LDL cholesterol (LDL-C) levels and coronary risk, it is possible that it brings on susceptibility to endothelial dysfunction and atherogenesis seen on uremia. Methods: Six hundred twenty patients were stratified according to glomerular filtration rate (GFR) estimated by Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) formula: group I > 60 mL/min, group II 15 mL/min, and group III <= 15 mL/min or in hemodialysis. Polymorphic ApoE analysis was performed by polymerase chain reaction amplification (PCR). Plasma ADMA levels were measured by high performance liquid chromatography (HPLC). Groups were compared on clinical and laboratory characteristics as well as allele and genotype distribution towards. Results: The epsilon 2 allele of ApoE was present in 62 (10.3 %) patients, epsilon 3 allele in 581 (96.2 %), and epsilon 4 allele in 114 (18.9 %). Their distribution among the 3 groups was uniform. Such uniformity was not observed when we considered endothelial function measured by asymmetric dimethylarginine. In group III, the frequency of epsilon 4 allele was significantly lower in the third tertile compared with the first tertile (14.7 versus 53.3 %, P = 0.000; Pearson chisquare). In groups I and II, there was no difference in allele frequency according to ADMA levels. This association remained significant even after confouding factors corrections (OR 0.329, 95 % CI 0.155 - 0.699, P = 0.004). Conclusions: The results of this study shows that the frequency of epsilon 4 allele of ApoE is significantly lower among hypertensive patients on hemodialysis with the highest levels of ADMA. Uremia is capable of determining lower plasma ADMA levels in hypertensive epsilon 4 allele carriers.Fundo de Amparo a Pesquisa do Estado de Sao Paulo/FAPESPUniv Fed Sao Paulo, Nephrol Div, R Pedro de Toledo 781 14 Andar, BR-04039032 Sao Paulo, BrazilTufts Univ, New England Med Ctr, Nephrol Div, Boston, MA 02111 USAHosp Israelita Albert Einstein, Res & Educ Inst, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Nephrol Div, R Pedro de Toledo 781 14 Andar, BR-04039032 Sao Paulo, BrazilWeb of Scienc

Biocompatibility of a Conjugated Polymer Retinal Prosthesis in the Domestic Pig

The progressive degeneration of retinal photoreceptors is one of the most significant causes of blindness in humans. Conjugated polymers represent an attractive solution to the field of retinal prostheses, and a multi-layer fully organic prosthesis implanted subretinally in dystrophic Royal College of Surgeons (RCS) rats was able to rescue visual functions. As a step toward human translation, we report here the fabrication and in vivo testing of a similar device engineered to adapt to the human-like size of the eye of the domestic pig, an excellent animal paradigm to test therapeutic strategies for photoreceptors degeneration. The active conjugated polymers were layered onto two distinct passive substrates, namely electro-spun silk fibroin (ESF) and polyethylene terephthalate (PET). Naive pigs were implanted subretinally with the active device in one eye, while the contralateral eye was sham implanted with substrate only. Retinal morphology and functionality were assessed before and after surgery by means of in vivo optical coherence tomography and full-field electroretinogram (ff-ERG) analysis. After the sacrifice, the retina morphology and inflammatory markers were analyzed by immunohistochemistry of the excised retinas. Surprisingly, ESF-based prostheses caused a proliferative vitreoretinopathy with disappearance of the ff-ERG b-wave in the implanted eyes. In contrast, PET-based active devices did not evoke significant inflammatory responses. As expected, the subretinal implantation of both PET only and the PET-based prosthesis locally decreased the thickness of the outer nuclear layer due to local photoreceptor loss. However, while the implantation of the PET only substrate decreased the ff-ERG b-wave amplitude with respect to the pre-implant ERG, the eyes implanted with the active device fully preserved the ERG responses, indicating an active compensation of the surgery-induced photoreceptor loss. Our findings highlight the possibility of developing a new generation of conjugated polymer/PET-based prosthetic devices that are highly biocompatible and potentially suitable for subretinal implantation in patients suffering from degenerative blindnes

Validation of the Italian version of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire

Objectives The primary objective of this study was the translation and validation of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire into Italian, denoted as AAV-PRO_ita. The secondary objective was to evaluate the impact of ANCA-associated vasculitis (AAV) on quality of life (QoL) and work impairment in a large cohort of Italian patients. Methods The study design took a prospective cohort study approach. First, the AAV-PRO was translated into Italian following the step guidelines for translations. The new AAV-PRO_ita questionnaire covered three disease domains: organ-specific and systemic symptoms and signs; physical function; and social and emotional impact. Second, Italian-speaking AAV patients were recruited from 17 Italian centres belonging to the Italian Vasculitis Study Group. Participants completed the AAV-PRO_ita questionnaire at three time points. Participants were also requested to complete the work productivity and activity impairment: general health questionnaire. Results A total of 276 AAV patients (56.5% women) completed the questionnaires. The AAV-PRO_ita questionnaire demonstrated a good internal consistency and test-retest reliability. Female AAV patients scored higher (i.e. worse) in all thee domains, especially in the social and emotional impact domain (P &lt; 0.001). Patients on glucocorticoid therapy (n = 199) had higher scores in all domains, especially in the physical function domain (P &lt; 0.001), compared with patients not on glucocorticoid therapy (n = 77). Furthermore, patients who had at least one relapse of disease (n = 114) had higher scores compared with those who had never had one (n = 161) in any domain (P &lt; 0.05). Finally, nearly 30% of the patients reported work impairment. Conclusion The AAV-PRO_ita questionnaire is a new 29-item, disease-specific patient-reported outcome measuring tool that can be used in AAV research in the Italian language. Sex, glucocorticoids and relapsing disease showed the greatest impact on QoL

PTX3 Intercepts Vascular Inflammation in Systemic Immune-Mediated Diseases

PTX3 is a prototypic soluble pattern recognition receptor, expressed at sites of inflammation and involved in regulation of the tissue homeostasis. PTX3 systemic levels increase in many (but not all) immune-mediated inflammatory conditions. Research on PTX3 as a biomarker has so far focused on single diseases. Here, we performed a multi-group comparative study with the aim of identifying clinical and pathophysiological phenotypes associated with PTX3 release. PTX3 concentration was measured by ELISA in the plasma of 366 subjects, including 96 patients with giant cell arteritis (GCA), 42 with Takayasu's arteritis (TA), 10 with polymyalgia rheumatica (PMR), 63 with ANCA-associated systemic small vessel vasculitides (AAV), 55 with systemic lupus erythematosus (SLE), 21 with rheumatoid arthritis (RA) and 79 healthy controls (HC). Patients with SLE, AAV, TA and GCA, but not patients with RA and PMR, had higher PTX3 levels than HC. PTX3 concentration correlated with disease activity, acute phase reactants and prednisone dose. It was higher in females, in patients with recent-onset disease and in those with previous or current active vasculitis at univariate analysis. Active small- or large- vessel vasculitis were the main independent variables influencing PTX3 levels at multivariate analysis. High levels of PTX3 in the blood can contribute to identify an increased risk of vascular involvement in patients with systemic immune-mediated diseases

Chronic constipation diagnosis and treatment evaluation: The "CHRO.CO.DI.T.E." study

Background: According to Rome criteria, chronic constipation (CC) includes functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). Some patients do not meet these criteria (No Rome Constipation, NRC). The aim of the study was is to evaluate the various clinical presentation and management of FC, IBS-C and NRC in Italy. Methods: During a 2-month period, 52 Italian gastroenterologists recorded clinical data of FC, IBS-C and NRC patients, using Bristol scale, PAC-SYM and PAC-QoL questionnaires. In addition, gastroenterologists were also asked to record whether the patients were clinically assessed for CC for the first time or were in follow up. Diagnostic tests and prescribed therapies were also recorded. Results: Eight hundred seventy-eight consecutive CC patients (706 F) were enrolled (FC 62.5%, IBS-C 31.3%, NRC 6.2%). PAC-SYM and PAC-QoL scores were higher in IBS-C than in FC and NRC. 49.5% were at their first gastroenterological evaluation for CC. In 48.5% CC duration was longer than 10 years. A specialist consultation was requested in 31.6%, more frequently in IBS-C than in NRC. Digital rectal examination was performed in only 56.4%. Diagnostic tests were prescribed to 80.0%. Faecal calprotectin, thyroid tests, celiac serology, breath tests were more frequently suggested in IBS-C and anorectal manometry in FC. More than 90% had at least one treatment suggested on chronic constipation, most frequently dietary changes, macrogol and fibers. Antispasmodics and psychotherapy were more frequently prescribed in IBS-C, prucalopride and pelvic floor rehabilitation in FC. Conclusions: Patients with IBS-C reported more severe symptoms and worse quality of life than FC and NRC. Digital rectal examination was often not performed but at least one diagnostic test was prescribed to most patients. Colonoscopy and blood tests were the "first line" diagnostic tools. Macrogol was the most prescribed laxative, and prucalopride and pelvic floor rehabilitation represented a "second line" approach. Diagnostic tests and prescribed therapies increased by increasing CC severity