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Regarding the first question, however, we believe that there is a clear answer in the article itself. We stated, in the Methods section, that “the biopsy specimens were assessed in Palermo by 2 pathologists (G.G. and/or A.M.F.)”; the eosinophil count, which seems to be one of the most important findings of the study, “was further assessed by an experienced gastrointestinal pathologist (V.V.) in Brescia.” We also added that “all reviewers were blinded to the diet allocation and final diagnosis of each patient.” Consequently, the k value provided in the Results section referred to the agreement between the evaluation performed in Palermo and the evaluation performed in Brescia. No further details were given in Supplementary Appendix 2 regarding this point. As far as the reference method for the eosinophil count is concerned, we thank Professor Weiner for his question and the opportunity given to us to be more precise. We quoted the Walker and Talley report because in this extensive review it clearly was stated that “normal duodenal counts (of eosinophils) are defined as fewer than 10 HPF [high-power fields] in children and 19/5 HPF in adults, in studies based on control values”; to be precise, the review was referring to another study here. The point of interest is that this upper limit (19 per 5 high-power fields) is almost identical to the one indicated in our laboratory: 40 lamina propria eosinophils per 10 high-power fields. In the rectal biopsy specimens, the upper limit of the reference interval was fewer than 9 lamina propria eosinophils per 5 high-power fields. This was an internal reference for our laboratory and the method was similar to that described by one of the review authors (V.V.) in children, and validated by another author (A.C.) in adults. In any case, a recent review underlined the problem of the cut-off value of eosinophils in the different gastrointestinal tract segments. On the topic of the possible role of mast cells in causing the irritable bowel syndrome (IBS)-like symptoms, we found a trend toward higher values in the nonceliac wheat sensitivity (NCWS) patients than in the non-NCWS controls, although the difference was not statistically significant. On the other hand, despite some relevant evidence for a mast cell role in IBS, it has been shown that increased mast cells are not present homogeneously throughout the whole colon mucosa because the increase was detected in the cecum but not in the left colon. Other studies have shown that a significant mast cell infiltration could be detected only in IBS patients with constipation, but not with diarrhea. Furthermore, the relevance of a concomitant presence of eosinophils that, in turn, activate mast cells, has been underlined. Thus, we did not exclude a possible role for mast cells in the pathogenesis of IBS-like symptoms in NCWS patients, but future studies need to be designed to better focus on this point. Finally, we suggested a possible clinical role for the eosinophil count in NCWS. In fact, as underlined in the Editorial that accompanied our article, our findings showed that “the sensitivity and specificity of the presence of rectal eosinophilia (>9 eosinophils in the rectal lamina propria) was 94% and 70%, respectively, and a positive and negative predictive value for true NCGS of 81% and 89%, respectively.” Obviously, this does not mean that an increased number of eosinophils in the rectal mucosa is equivalent to a NCWS diagnosis, but that in the absence of endoscopic findings and/or other obvious causes (ie, parasitic infection), an eosinophil infiltration could be a marker of NCWS and must address the clinician to consider prescribing an elimination diet in subjects with suspected NCWS, as also was confirmed in a recent publication on the matter. In conclusion, we by no means presume to have found “the diagnostic marker of NCWS,” but we think rather that we have suggested a candidate pathogenetic player (the eosinophil) and a target intestinal site (the rectum) for NCWS disease. These are relevant clinical data to be investigated further in future studies
Non-celiac wheat sensitivity: rationality and irrationality of a gluten-free diet in individuals affected with non-celiac disease: a review
Non-celiac gluten or wheat sensitivity (NCWS) is a “clinical entity induced by the ingestion of wheat leading to intestinal and/or extraintestinal symptoms that improve once the wheat-containing foodstuff is removed from the diet, and celiac disease and wheat allergy have been excluded”. This mostly accepted definition raises several points that remain controversial on this condition. In the present review, the authors summarize the most recent advances in the clinic and research on NCWS through an accurate analysis of different studies. We screened PubMed, Medline, Embase, and Scopus using the keywords “non-celiac gluten sensitivity”, “non-celiac wheat sensitivity”, and “diagnosis”. We would like to emphasize two main points, including (A) the controversial clinical and etiological aspects in different trials and experiences with particular attention to the Salerno criteria for the diagnosis of NCWS and (B) the histological aspects. The etiology of NCWS remains controversial, and the relationship with irritable bowel syndrome is obscure. Histologically, the duodenal mucosa may show a variable pattern from unremarkable to a slight increase in the number of T lymphocytes in the superficial epithelium of villi. The endorsement of this disease is based on a positive response to a gluten-free diet for a limited period, followed by the reappearance of symptoms after gluten challenge. The Salerno expert criteria may help to diagnose NCWS accurately. Social media and inaccurate interpretation of websites may jeopardize the diagnostic process if individuals self-label as gluten intolerant
Pediatric noncoeliac gluten sensitivity
Functional gastrointestinal disorders remain a rather obscure and vague chapter of medicine, clouded with discordant, or even completely contradictory findings and opinions, depending on the different researchers and studies. The two main etiological hypotheses are an alteration of the brain-gut axis with visceral hypersensitivity, or a microscopic inflammation of the gastro-intestinal mucosa. However, what appears to link these and other hypotheses is the evidence that the symptoms reported by patients, both in adults and in the pediatric age, are very often presented in association with the intake of specific foods. To further complicate this heterogeneous situation, several authors have reported cases of patients without the celiac disease (CeD) or wheat allergy (WA) criteria, who referred a marked improvement in gastro-intestinal functional symptoms on a gluten-free diet (GFD). This condition was initially defined as ‘gluten sensitivity’ (GS), only to be changed to ‘non-celiac gluten sensitivity’ (NCGS), to better differentiate it from CeD, and finally redefined as ‘non-celiac wheat sensitivity’ (NCWS), as it is still not certain even today which of the components of wheat is the real culprit of this pathology. To date, this is one of the most studied and controversial areas of research in the gastroenterological field, with data that, at least in part, seem to indicate that NCGS/NCWS in adults could represent a form of non-IgE-mediated allergic reaction that has its roots in some clinical reactions already in the pediatric ag
Screening for celiac disease in patients with chronic liver disease
Dear Sir:We read with interest the paper of Kaukinen et al. reporting anelevated frequency of celiac disease (CD) (4.3%) in patients with previousliver transplantation due to severe hepatic dysfunction.1However, wewould like to report our experience of the serologic assays for CDdiagnosis in patients with chronic liver disease and comment on thescreening methods for CD used in that study. Between January andOctober 2001, we studied 96 consecutive subjects (65 male, 31 female,age range 18–87 years, median 42) with chronic hypertransaminasemiawho were attending for thefirst time the outpatients clinic for liverdisease at the Internal Medicine Division of the University Hospital ofPalermo. All patients underwent a complete work-up including routineliver function tests, serologic screening for viral hepatitis, presence ofserum autoantibodies, copper- and iron-related indexes,1-antitrypsinlevels, liver ultrasonography, and percutaneous liver biopsy. We foundchronic hepatitis in 70 cases, liver cirrhosis in 20 patients, nonalcoholicsteatohepatitis in 3 patients, and primary biliary cirrhosis in 3 patients.In all cases, serological screening for CD was also performed by deter-mining the values of total immunoglobulin (to exclude selective IgAdeficiency), IgA class anti-endomysial antibody (EmA) using monkey’sesophagus as the substrate, and IgA class anti-human transglutaminaseantibody (Anti-tTG). Both the serum EmA and anti-tTG assays wereperformed with commercially available assays as previously described andthe threshold value for serum anti-tTG was7%.2We found 3 of 96patients positive for serum anti-tTG, but only one of them was positivefor serum EmA. This last patient, an 18-year-old girl, had mild chronichepatitis due to hepatitis B virus; she had never reported gastrointestinalsymptoms or anemia and her body mass index was normal. She under-went the duodenal biopsy and the histology study, performed as previ-ously described,3which showed severe atrophy of the mucosa (villi/cryptsratio 0.5) with an elevated intraepithelial lymphocytes count, thus con-firming the CD diagnosis. The 2 other patients, positive for serumanti-tTG but negative for EmA, had mild chronic hepatitis and livercirrhosis respectively, both due to hepatitis C virus infection. These 2patients accepted to undergo the intestinal biopsy but their intestinalhistology was normal (villi/crypts ratio3.5, normal intraepitheliallymphocytes count). Furthermore, both these patients were negative forthe presence of the HLA-DQ2 and HLA-DQ8 antigens, which charac-terize CD patients. The 2 patients with false positive anti-tTG results didnot differ from all the other subjects included in the study with regard toliver histology grading and staging, severity of liver function impair-ment, serum-globulin, and etiology of the liver disease. Furthermore,both were negative for serum auto-antibodies. In total, we consequentlyfound 1% frequency of CD and 2% of false positive anti-tTG results forCD diagnosis in our group of patients with chronic liver disease.Kaukinen et al. reported a much higher frequency of CD (4.3%)very probably linked to the high frequency of autoimmune liverdisease (primary biliary cirrhosis, primary sclerosing cholangitis, au-toimmune hepatitis) in their series.1However, although our dataindicated that the frequency of CD was lower in consecutive patientswith chronic liver disease, not including exclusively subjects withend-stage liver disease, we think that CD screening should be per-formed in any case as Kaukinen et al. clearly demonstrated thatdietary treatment in CD patients may prevent the progression tohepatic failure.1In regard to the serologic screening for CD, in theFinnish study there was a 2-fold higher frequency of false positiveanti-tTG results (8 of 185 cases, 4.3%) than in our study. This wasprobably in part due to the use of an anti-tTG ELISA based on tTGfrom guinea pig liver as the antigen4; in fact, we have previouslydemonstrated that in patients with chronic liver disease this systemgives a higher number of false positive results than the anti-tTGELISA based on human recombinant tTG as the antigen and shouldnot be used as a screening tool for CD.5However, our present dataunderlined that in patients with chronic liver diseases, false positiveanti-tTG results can also be observed using the anti-tTG assay basedon human antigen. Consequently, we suggest that when EmA assay doesnot confirm the positivity of the anti-tTG assay, determination of theHLA haplotype should be the subsequent step and only DQ2 or DQ8positive subjects should undergo intestinal biopsy for CD diagnosis
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Gluten Intolerance and Sensitivityin the Elderly.
Celiac disease (CD) is a chronic, immune-mediated enteropathy in genetically predisposed individuals caused by the ingestion of gluten-containing cereals. CD is further characterized by variable clinical presentation, specific serum autoantibody response and a variable degree of damage in the small intestinal mucosa. HLA molecules DQ2 (90%–95%) and DQ8 (5%–10%) are associated with CD, and in the continued presence of gluten the disease is self-perpetuating. Regarding clinical presentation, CD patients may complain of not only gastrointestinal (GI) symptoms, but also extraintestinal symptoms, and most importantly they may often be asymptomatic (“silent” CD). In recent years, several reports have suggested a major shift in the clinical presentation of CD with extraintestinal symptoms being more prevalent than “classical” GI symptoms. CD is also associated with several autoimmune diseases, usually thyroiditis and diabetes mellitus type 1. Currently, the only effective treatment available is a strict life-long gluten-free diet (GFD), which improves symptoms, nutritional status, and serologic and histologic change
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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