Protocol design for randomized clinical trial to compare underwater cold snare polypectomy to conventional cold snare polypectomy for non-pedunculated colon polyps of size 5-10 mm (COLDWATER study).

BACKGROUND: Colorectal cancer is internationally the third leading cause of death from a malignant disease. The aim of screening colonoscopy in adults > 45 years of age is early diagnosis and treatment of precancerous polyps. Endoscopic polyp removal (polypectomy) can be achieved with various techniques depending on the size, morphology, and location of the polyp. According to current guidelines, small non-pedunculated polyps should be removed with a cold snare after the colorectal lumen has been insufflated with air (conventional cold snare polypectomy).In recent years, several studies have described the benefits of water aided colonoscopy, as well as the safety and efficacy of underwater cold snare polypectomy for large colon polyps. However, there are insufficient data on conventional and underwater techniques for small polyps, the most commonly diagnosed colorectal polyps. METHODS: We have designed a prospective randomized double-blind clinical trial to compare the safety and efficacy of conventional and underwater cold snare polypectomy for non-pedunculated polyps 5-10 mm in size. A total of 398 polyps will be randomized. Randomization will be carried out using the random numbers method of Microsoft Excel 2016. The primary endpoint is the muscularis mucosa resection rate. Secondary endpoints are the depth and percentage of R0 excisions, complications, and the recurrence rate at follow-up endoscopy 6-12 months after polypectomy. DISCUSSION: We hypothesize underwater polypectomy will result in a higher muscularis mucosa resection rate. The results of our study will provide useful data for the development of guidelines in polypectomy techniques for non-pedunculated polyps 5-10 mm in size. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT05273697.

Enhanced monocyte migration and pro-inflammatory cytokine production by Porphyromonas gingivalis infection.

BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis, a major periodontal pathogen, has been reported to be involved in atherogenesis. In order to further understand this pathogen's link with systemic inflammation and vascular disease, we investigated its influence on murine monocytes and macrophages from three different sources. MATERIAL AND METHODS: Concanavalin A-elicited peritoneal macrophages, peripheral blood monocyte-derived macrophages and WEHI 274.1 monocytes were infected with either P. gingivalis 381 or its non-invasive fimbriae-deficient mutant, DPG3. RESULTS: Infection with P. gingivalis 381 markedly induced monocyte migration and significantly enhanced production of the pro-inflammatory cytokines, tumor necrosis factor-alpha and interleukin-6. Consistent with a role for this pathogen's major fimbriae and/or its invasive capacity, infection with DPG3 had a minimal effect on both monocyte attraction and pro-inflammatory cytokine production. CONCLUSION: Since monocyte recruitment and activation are important steps in the development of vascular inflammation and atherosclerosis, these results suggest that P. gingivalis infection may be involved in these processes.

A micro-Raman and X-ray study of erupted submarine pyroclasts from El Hierro (Spain) and its' astrobiological implications.

The pumice volcanic samples could have possible connections to the evolution of life and give us insight about their bio-geochemical processes related. In this regard, the samples from the volcanic eruption from La Restinga (El Hierro, Spain) in 2011 have been mainly studied by means of Raman spectroscopy. The research also includes analysis of XRD, Scanning Electron Microscopy and Optical Microscopy to support the Raman analysis. The results show that the Raman methods and mineral analyses are in strong agreement with the results obtained from other authors and techniques. The internal white foamy core (WFC) of the studied pumice samples shows amorphous silica, Fe-oxides, Ti-oxides, quartz, certain sulfates, carbonates, zeolites and organics. On the other hand, the external part (dark crust - DC) of these samples mainly presents primary-sequence mineralogy combined with some secondary alteration minerals such as olivine, feldspar, pyroxene, amorphous silica, and Fe-oxide. Raman spectroscopy detected other minerals not yet reported on these samples like barite, celestine and lepidocrocite. Also, the different chemometric and calibration methods for Raman spectroscopy in elemental composition, mineral classification and structural characterization has been successfully applied. From the astrobiological perspective, the research was also complemented with comparisons to other similar samples from terrestrial analogs. The main consideration was taking into account the proposed hypothesis regarding the potential behavior of the pumice as a substrate for the evolution of life. Furthermore, the detailed analysis from La Restinga eruption is coherent with the mineral phases and processes discussed from previous literature. The white internal part fulfills the conditions to work as an organic reservoir, confirmed by the detection of organic matter and selected minerals that could be used as energy sources for bacterial communities. The external layers of the samples work as a shielding layer to protect the organics from decay in extreme conditions. Finally, here we have demonstrated that the characteristics and advantages of Raman spectroscopy could help to assess and understand the possible biogenicity and alteration processes of any geological sample to be found on Mars.

Intravenous immunoglobulins induce CD32-mediated platelet aggregation in vitro.

BACKGROUND: Intravenous immunoglobulins (IVIg) and cytomegalovirus immunoglobulins (CMVIg) are currently finding increased acceptance in clinical states of high immune activity and in transplant recipients. A rare side-effect of their application is intravascular thrombosis, which is thought to be related to pre-existing hyperviscosity. In a previous study we have shown that rabbit antithymocyte globulin causes platelet aggregation in vitro via the Fc IgG receptor (CD32). OBJECTIVES: To investigate if IVIg and CMVIg have the potential to cause CD32-dependent platelet aggregation. METHODS: The influence of CMVIg or IVIg on platelets pre-incubated with or without monoclonal antibody AT10 was studied in an aggregometer. Expression of platelet surface activation marker CD62P was determined by fluorescence-activated cell sorting analysis and presence of soluble CD40L (sCD40L) was evaluated by enzyme-linked immunosorbent assay. All in vitro experiments were performed using platelet concentrates from the blood bank, at therapeutic concentrations of immunoglobulins. Results Incubation of platelets with CMVIg and IVIg markedly induced platelet aggregation, and increased expression of CD62P and secretion of sCD40L. The capacity of CMVIg and IVIg to induce platelet aggregation was completely abrogated by adding the blocking antibody AT10 directed against the low-affinity Fc IgG receptor (CD32). CONCLUSIONS: Our results suggest that CMVIg and IVIg solutions with activating Fc domains are able to bind CD32 on platelets and cause platelet aggregation in vitro. These results indicate a mechanism by which in vivo intravascular thrombosis may be explained and suggest caution with concomitant use of packed platelets and IVIg in autoimmune diseases in the clinical setting.

Screening for Diabetes Risk Using Integrated Dental and Medical Electronic Health Record Data.

Undiagnosed diabetes and prediabetes present a serious public health challenge. We previously reported that data available in the dental setting can serve as a tool for early dysglycemia identification in a primarily Hispanic, urban population. In the present study, we sought to determine how the identification approach can be recalibrated to detect diabetes or prediabetes in a White, rural cohort and whether an integrated dental-medical electronic health record (iEHR) offers further value to the process. We analyzed iEHR data from the Marshfield Clinic, a health system providing care in rural Wisconsin, for dental patients who were ≥21 y of age, reported that they had never been told they had diabetes, had an initial periodontal examination of at least 2 quadrants, and had a glycemic assessment within 3 mo of that examination. We then assessed the performance of multiple predictive models for prediabetes/diabetes. The study outcome, glycemic status, was gleaned from the medical module of the iEHR based on American Diabetes Association blood test cutoffs. The sample size was 4,560 individuals. Multivariate logistic regression revealed that the best performance was achieved by a model that took advantage of the iEHR. Predictors included age, sex, race, ethnicity, number of missing teeth, percentage of teeth with at least 1 pocket ≥5 mm from the dental EHR, and overweight/obesity, hypertension, hyperlipidemia, and smoking status from the medical EHR. The model achieved an area under the receiver operating characteristic curve of 0.71 (95% confidence interval, 0.69-0.72), yielding a sensitivity of 0.70 and a specificity of 0.62. Across a range of populations, informed by certain patient characteristics, dental care team members can play a role in helping to identify dental patients with undiagnosed diabetes or prediabetes. The accuracy of the prediction increases when dental findings are combined with information from the medical EHR. Knowledge Transfer Statement: Prediabetes and diabetes often go undiagnosed for many years. Early identification and care can lead to improved glycemic outcomes and prevent wide-ranging morbidity, including adverse oral health consequences, in affected individuals. Information available in the dental office can be used by clinicians to identify those who remain undiagnosed or are at risk; the accuracy of this prediction increases when combined with information from the medical electronic health record.

Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice.

Diabetes is associated with increased prevalence, severity, and progression of periodontal disease. To test the hypothesis that activation of RAGE (Receptor for Advanced Glycation End products) contributes to the pathogenesis of diabetes-associated periodontitis, we treated diabetic mice, infected with the human periodontal pathogen Porphyromonas gingivalis, with soluble RAGE (sRAGE). sRAGE is the extracellular domain of the receptor, which binds ligand and blocks interaction with, and activation of, cell-surface RAGE. Blockade of RAGE diminished alveolar bone loss in a dose-dependent manner. Moreover, we noted decreased generation of the proinflammatory cytokines TNF-alpha and IL-6 in gingival tissue, as well as decreased levels of matrix metalloproteinases. Gingival AGEs were also reduced in mice treated with sRAGE, paralleling the observed suppression in alveolar bone loss. These findings link RAGE and exaggerated inflammatory responses to the pathogenesis of destructive periodontal disease in diabetes.

Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model.

Although hyperhomocysteinemia (HHcy) is a well-known risk factor for the development of cardiovascular disease, the underlying molecular mechanisms are not fully elucidated. Here we show that induction of HHcy in apoE-null mice by a diet enriched in methionine but depleted in folate and vitamins B6 and B12 increased atherosclerotic lesion area and complexity, and enhanced expression of receptor for advanced glycation end products (RAGE), VCAM-1, tissue factor, and MMP-9 in the vasculature. These homocysteine-mediated (HC-mediated) effects were significantly suppressed, in parallel with decreased levels of plasma HC, upon dietary supplementation with folate and vitamins B6/B12. These findings implicate HHcy in atherosclerotic plaque progression and stability, and they suggest that dietary enrichment in vitamins essential for the metabolism of HC may impart protective effects in the vasculature.

Infection with a periodontal pathogen induces procoagulant effects in human aortic endothelial cells.

BACKGROUND: Multiple studies have demonstrated a link between periodontal infections and vascular disease. Porphyromonas gingivalis, a major periodontal pathogen, has been shown to adhere to and invade endothelial cells. OBJECTIVE: In order to dissect mechanisms underlying these observations, we assessed the role of P. gingivalis infection in modulating properties of endothelial cells linked to atherothrombosis. METHODS: Primary human aortic endothelial cells (HAEC) were infected with either P. gingivalis 381 or its non-invasive fimbriae-deficient mutant, DPG3. Markers of coagulation and thrombosis were assessed 8 h and 18 h postinfection in cell lysates and supernatants. RESULTS: Infection with P. gingivalis 381 significantly enhanced tissue factor expression and activity, and suppressed levels of tissue factor pathway inhibitor. Furthermore, P. gingivalis infection decreased levels and activity of tissue plasminogen activator, and enhanced plasminogen activator inhibitor-1 antigen and activity. Consistent with an important role for bacterial adhesion/invasion in this setting, infection with DPG3 failed to induce procoagulant properties in HAEC. Most of the above effects of P. gingivalis 381 were more apparent at the later time point (18 h postinfection). This suggests that P. gingivalis infection, rather than having an immediate and direct effect, might activate pathways that, in turn, trigger endothelial procoagulant mechanisms. CONCLUSIONS: Taken together these data demonstrate for the first time that infection with a periodontal pathogen induces procoagulant responses in HAEC.

[Instrumental diagnosis in shoulder instability]. / La diagnostica strumentale nell'instabilità di spalla.

The authors call attention to the pathology caused by glenohumeral instability and, in particular, to painful shoulders in athletes which so often cause problems in diagnosis. An instrumental protocol for diagnosis is suggested, based on several specific radiographic views, Ct scan and arthro-Ct scan, with double contrast medium, the latter having the task of determining lesion which would not otherwise be able to be studied.

[A modified Putti-Platt surgical method in the treatment of habitual luxation of the anterior shoulder: our experience]. / L'intervento di Putti-Platt modificato nel trattamento della lussazione anteriore abituale di spalla: nostra esperienza.

Fifty cases of recurrent dislocation of the shoulder operated according to the Putti-Platt method modified by lateralization of the insertion of the coracoid processes are reported. Excellent results were obtained in 86% of the cases. There was neither incidence of recurrence, nor degenerative joint alteration. Mild limitation in extrarotation (less than 10 degrees) was observed in 7 cases.

[Osteitis condensans ilii: therapy and diagnostic problems. Presentation of a case study]. / L'osteite condensante dell'ileo: Problemi di diagnosi e terapia. Contributo casistico.

The authors describe 4 female patients with Osteitis Condensans Ilii (OCI): 3 of them were pluriparous, ranging 32-36 years of age; while the remaining was nulliparous and 20 years old, with a previous trauma suffered in the iliac bone. Due to the inefficacy of the medical and physical treatment, two patients underwent surgical resection of the osteitic bone; then followed by a 45 days cast immobilization and a 3-4 months with restricted load. The other 2 patients were successfully treated with Indomethacin (a 100 mg/day cycle for a month, followed by a maintainance cycle with 300 mg/day for 3 months). The diagnostic aspects are then discussed, pointing out that absence of any peripheric neurologic damage, normal bone scan, female sex and younger age are the relevant characteristics for the diagnosis of OCI.

Periodontitis and systemic disease.

Recent evidence suggests that periodontal disease may play an etiologic role in the pathogenesis of several systemic illnesses, such as cardiovascular disease and preterm birth. This article reviews proposed mechanisms for such associations and outlines studies currently underway aimed at clarifying this issue. Results from this line of research may fundamentally change the way we approach our periodontitis patients.

Dental findings and identification of undiagnosed hyperglycemia.

A change in the American Diabetes Association guidelines added hemoglobin A1c (HbA1c) to the assays for diabetes diagnosis, but evidence suggests that glucose vs. HbA1c criteria may identify different segments of the affected population. We previously demonstrated that oral findings offer an opportunity for the detection of undiagnosed abnormal fasting plasma glucose (FPG) among dental patients who present with diabetes risk factors. In this new cross-sectional study, we sought to extend these observations. The first goal, using data from 591 new participants, was to assess our previously identified hyperglycemia detection models when HbA1c is used for case definition. The second goal, using data from our total cohort of 1,097 participants, was to evaluate the models' performance regardless of whether an FPG or an HbA1c is used for diagnosis. The presence of ≥ 26% teeth with deep pockets or ≥ 4 missing teeth correctly identified 72% of pre-diabetes or diabetes cases in the HbA1c sample and 75% in the total population. The addition of a point-of-care HbA1c ≥ 5.7% increased correct identification to 87% and 90%, respectively. These results demonstrate the validity of our prediction models regardless of the test used for diabetes or pre-diabetes diagnosis in the clinical setting and underscore the contribution dentists can make.

Identification of unrecognized diabetes and pre-diabetes in a dental setting.

Many diabetic patients remain undiagnosed, and oral findings may offer an unrealized opportunity for the identification of affected individuals unaware of their condition. We recruited 601 individuals who presented for care at a dental clinic, were ≥40 years old, if non-Hispanic white, and ≥30 years old, if Hispanic or non-white, and had never been told they have pre-diabetes or diabetes. Those with at least one self-reported diabetes risk factor (N=535) received a periodontal examination and a point-of-care hemoglobin A1c (HbA1c) test. A fasting plasma glucose (FPG) test was used as the study outcome, signifying potential diabetes or pre-diabetes. Performance characteristics of simple models of dysglycemia (FPG≥100 mg/dL) identification were evaluated and optimal cut-offs identified. A model including only two dental variables had an estimated area under the receiver operating characteristic curve (AUC) of 0.65. The addition of a point-of-care HbA1c test improved the AUC to 0.79 (p<0.001). The presence of ≥26% deep pockets or ≥4 missing teeth correctly identified 73% of true cases; the addition of an HbA1c≥5.7% increased correct identification to 92%. Analysis of our data suggests that oral healthcare professionals have the opportunity to identify unrecognized diabetes and pre-diabetes in dental patients and refer them to a physician for further evaluation and care.

Diabetes in the dental office: using NHANES III to estimate the probability of undiagnosed disease.

BACKGROUND AND OBJECTIVE: Recent data have suggested that in the past 15 years there has been a dramatic increase in the incidence of diabetes mellitus in the USA. However, evidence suggests that approximately one-third of diabetes cases remain undiagnosed. Because 60% of Americans see a dentist at least once per year for routine, nonemergent, care, it is reasonable to propose that the dental office can be a healthcare location actively involved in screening for unidentified diabetes. MATERIAL AND METHODS: This study used NHANES III to develop a predictive equation that can form the basis of a tool to help dentists determine the probability of undiagnosed diabetes by using self-reported data and periodontal clinical parameters routinely assessed in the dental office. RESULTS: Our analyses reveal that individuals with a self-reported family history of diabetes, hypertension, high cholesterol levels and clinical evidence of periodontal disease bear a probability of 27-53% of having undiagnosed diabetes, with Mexican-American men exhibiting the highest probability and white women the lowest. CONCLUSION: These findings suggest that the dental office could provide an important opportunity to identify individuals unaware of their diabetic status.

Effects of periodontal therapy on serum C-reactive protein, sE-selectin, and tumor necrosis factor-alpha secretion by peripheral blood-derived macrophages in diabetes. A pilot study.

BACKGROUND AND OBJECTIVE: Diabetes is associated with an increased risk for vascular disease and periodontitis. The aim of this study was to assess the effects of periodontal treatment in diabetes with respect to alterations in the pro-inflammatory potential of peripheral blood mononuclear cells. MATERIAL AND METHODS: Ten patients with diabetes and moderate to severe periodontitis received full-mouth subgingival debridement. Blood samples for serum/plasma and mononuclear cell isolation were collected prior to and 4 wk after therapy. Mononuclear cells were analyzed by flow cytometry and stimulated with lipopolysaccharide or ionomycin/phorbol ester to determine the pro-inflammatory capacity of macrophages and lymphocytes, respectively. RESULTS: Following periodontal treatment, all patients demonstrated a significant improvement in clinical periodontal status (p < 0.05), despite only modest reduction in subgingival bacterial load or homologous serum immunoglobulin G titers. CD14(+) blood monocytes decreased by 47% (p < 0.05), and the percentage of macrophages spontaneously releasing tumor necrosis factor-alpha decreased by 78% (p < 0.05). There were no significant changes in the capacity of lymphocytes to secrete interferon-gamma. Among a number of serum inflammatory markers tested, high-sensitivity-C-reactive protein significantly decreased by 37% (p < 0.01) and soluble E-selectin decreased by 16.6% (p < 0.05). CONCLUSION: These data suggest a reduced tendency for monocyte/macrophage-driven inflammation with periodontal therapy and a potential impact on atherosclerosis-related complications in diabetic individuals.

Diabetes-related parameters and periodontal conditions in children.

BACKGROUND AND OBJECTIVE: The relationship between diabetes and periodontal diseases is well established. Our aim in this study was to explore the diabetes-related parameters that are associated with accelerated periodontal destruction in diabetic youth. MATERIAL AND METHODS: Three-hundred and fifty 6-18-year-old children with diabetes received a periodontal examination. Data on important diabetes-related variables were collected. Analyses were performed using logistic regression, with gingival/periodontal disease as the dependent variable, for the whole cohort and separately for two subgroups (6-11 and 12-18 years of age). RESULTS: Regression analyses, adjusting for age, gender, ethnicity, frequency of prior dental visits, dental plaque, and dental examiner, revealed a strong positive association between mean hemoglobin A1c over the 2 years prior to inclusion in the study and periodontitis (odds ratio = 1.31, p = 0.030). This association approached significance in the younger subgroup (odds ratio = 1.56, p = 0.052, n = 183). There was no significant relationship between diabetes duration or body mass index-for-age and measures of gingival/periodontal disease in this cohort. CONCLUSION: These findings suggest that accelerated periodontal destruction in young people with diabetes is related to the level of metabolic control. Good metabolic control may be important in addressing periodontal complications in young patients with diabetes, similarly to what is well established for other systemic complications of this disease.

Enhanced interaction of advanced glycation end products with their cellular receptor RAGE: implications for the pathogenesis of accelerated periodontal disease in diabetes.

The prevalence and severity of periodontal disease is increased in patients with both insulin-deficient and insulin-resistant forms of diabetes. While a number of underlying factors likely contribute to enhanced periodontal inflammation and alveolar bone loss in diabetes, a common characteristic of these disorders, regardless of etiology, is the presence of hyperglycemia. A critical consequence of hyperglycemia is non-enzymatic glycation and oxidation of proteins and lipids. After a series of reversible reactions which lead to the generation of Schiff bases/Amadori products, a further series of complex molecular rearrangements ensues which results in the formation of the irreversible advanced glycation end products, or AGEs. AGEs accumulate during the process of normal aging in the plasma and tissues, but to an accelerated degree in patients with diabetes. A central means by which AGEs are believed to impart their pathogenic effects is via interaction with specific cellular receptors; the best-characterized of these is receptor for AGE, or RAGE. RAGE, a member of the immunoglobulin superfamily of cell surface molecules, is present in increased levels on target cells in diabetes, such as endothelial cells and monocytes. One consequence of AGE-RAGE interaction is the generation of enhanced cellular oxidant stress, a means by which cell signaling pathways may be activated, thereby resulting in altered cellular phenotype and cellular dysfunction. In this report, we will review our studies to date on AGEs and RAGE and consider the implications of their enhanced interaction in the pathogenesis of accelerated periodontal disease in diabetes.