Quantitative 3D-KPFM imaging with simultaneous electrostatic force and force gradient detection.

Kelvin probe force microscopy (KPFM) is a powerful characterization technique for imaging local electrochemical and electrostatic potential distributions and has been applied across a broad range of materials and devices. Proper interpretation of the local KPFM data can be complicated, however, by convolution of the true surface potential under the tip with additional contributions due to long range capacitive coupling between the probe (e.g. cantilever, cone, tip apex) and the sample under test. In this work, band excitation (BE)-KPFM is used to negate such effects. In contrast to traditional single frequency KPFM, multifrequency BE-KPFM is shown to afford dual sensitivity to both the electrostatic force and the force gradient detection, analogous to simultaneous amplitude modulated and frequency modulated KPFM imaging. BE-KPFM is demonstrated on a Pt/Au/SiO(x) test structure and electrostatic force gradient detection is found to lead to an improved lateral resolution compared to electrostatic force detection. Finally, a 3D-KPFM imaging technique is developed. Force volume (FV) BE-KPFM allows the tip-sample distance dependence of the electrostatic interactions (force and force gradient) to be recorded at each point across the sample surface. As such, FVBE-KPFM provides a much needed pathway towards complete tip-sample capacitive de-convolution in KPFM measurements and will enable quantitative surface potential measurements with nanoscale resolution.

Breaking the limits of structural and mechanical imaging of the heterogeneous structure of coal macerals.

The correlation between local mechanical (elasto-plastic) and structural (composition) properties of coal presents significant fundamental and practical interest for coal processing and for the development of rheological models of coal to coke transformations. Here, we explore the relationship between the local structural, chemical composition, and mechanical properties of coal using a combination of confocal micro-Raman imaging and band excitation atomic force acoustic microscopy for a bituminous coal. This allows high resolution imaging (10s of nm) of mechanical properties of the heterogeneous (banded) architecture of coal and correlating them to the optical gap, average crystallite size, the bond-bending disorder of sp(2) aromatic double bonds, and the defect density. This methodology allows the structural and mechanical properties of coal components (lithotypes, microlithotypes, and macerals) to be understood, and related to local chemical structure, potentially allowing for knowledge-based modeling and optimization of coal utilization processes.

Open loop Kelvin probe force microscopy with single and multi-frequency excitation.

Conventional Kelvin probe force microscopy (KPFM) relies on closed loop (CL) bias feedback for the determination of surface potential (SP). However, SP measured by CL-KPFM has been shown to be strongly influenced by the choice of measurement parameters due to non-electrostatic contributions to the input signal of the bias feedback loop. This often leads to systematic errors of several hundred mV and can also result in topographical crosstalk. Here, open loop (OL)-KPFM modes are investigated as a means of obtaining a quantitative, crosstalk free measurement of the SP of graphene grown on Cu foil, and are directly contrasted with CL-KPFM. OL-KPFM operation is demonstrated in both single and multi-frequency excitation regimes, yielding quantitative SP measurements. The SP difference between single and multilayer graphene structures using OL-KPFM was found to be 63 ± 11 mV, consistent with values previously reported by CL-KPFM. Furthermore, the same relative potential difference between Al2O3-coated graphene and Al2O3-coated Cu was observed using both CL and OL techniques. We observed an offset of 55 mV between absolute SP values obtained by OL and CL techniques, which is attributed to the influence of non-electrostatic contributions to the input of the bias feedback used in CL-KPFM.

[Prevalence of dermatological diseases in Primary Care]. / Prevalencia de enfermedades dermatológicas en atención primaria.

OBJECTIVE: To guide the training of Primary Care physicians in the most prevalent and relevant skin pathologies, it is necessary to study their prevalence in the Primary Care consultation and describe their characteristics. MATERIALS AND METHODS: Observational cross-sectional study. It took place at the Porriño Health Center (Pontevedra, Spain). A total of 305 patients of the same quota participated, recruited in consultation during 41days between September 2018 and February 2019, selected by systematic sampling coinciding with those mentioned at the hour between 9 and 13hours and, failing that, we selected the next of those mentioned. The variables were analyzed: age, sex, educational and economic level, diagnostic means, previous diagnosis of dermatological disease, treatment, follow-up and relationship with systemic diseases. The statistical analysis performed was descriptive and bivariate by sex with chi-square and Fisher's exact tests. RESULTS: 161 women and 144 men participated, age and number of consultations being non-parametric. Median age was 59years (IQR: 42-69), with no significant differences between sexes. 69.83% (95%CI: 64.46-74.71) present between 1 and 5 types of skin lesions grouped in 33 different diagnoses. The 15 most frequent pathologies account for 77.35% (95%CI: 75.80-84.48) of diagnoses. As the most relevant pathologies, we observed two basal cell carcinomas and one squamous cell carcinoma (0.98%; 95%CI: 0.34-2.85). CONCLUSIONS: Dermatological diseases have a high prevalence in Primary Care.

Resolution theory, and static and frequency-dependent cross-talk in piezoresponse force microscopy.

Probing the functionality of materials locally by means of scanning probe microscopy (SPM) requires a reliable framework for identifying the target signal and separating it from the effects of surface morphology and instrument non-idealities, e.g. instrumental and topographical cross-talk. Here we develop a linear resolution theory framework in order to describe the cross-talk effects, and apply it for elucidation of frequency-dependent cross-talk mechanisms in piezoresponse force microscopy. The use of a band excitation method allows electromechanical/electrical and mechanical/topographic signals to be unambiguously separated. The applicability of a functional fit approach and multivariate statistical analysis methods for identification of data in band excitation SPM is explored.

Intrinsic single-domain switching in ferroelectric materials on a nearly ideal surface.

Ferroelectric domain nucleation and growth in multiferroic BiFeO(3) is studied on a single-domain level by using piezoresponse force spectroscopy. Variation of local electromechanical response with dc tip bias is used to determine the size of the domain formed below the conductive scanning probe tip. The domain parameters are calculated self-consistently from the decoupled Green function theory by using tip geometry determined from the domain wall profile. The critical parameters of the nucleating domain and the activation energy for nucleation are determined. The switching mechanism is modeled by using the phase-field method, and comparison with experimental results shows that the nucleation biases are within a factor of approximately 2 of the intrinsic thermodynamic limit. The role of atomic-scale defects and long-range elastic fields on nucleation bias lowering is discussed. These measurements open a pathway for quantitative studies of the role of a single defect on kinetics and thermodynamics of first order bias-induced phase transitions and electrochemical reactions.

Macroscopic small bowel mucosal injury caused by chronic nonsteroidal anti-inflammatory drugs (NSAID) use as assessed by capsule endoscopy.

OBJECTIVE: To evaluate the type, frequency, and severity of macroscopic small bowel mucosal injury after chronic NSAID intake as assessed by capsule endoscopy (CE), as well as to correlate the severity of gastroduodenal and intestinal damage in these patients. MATERIAL AND METHODS: A prospective, endoscopist-blind, controlled trial. Sixteen patients (14F/2M; age: 57.06 +/- 10.16 yrs) with osteoarthritis (OA) on chronic therapy with NSAIDs underwent CE and upper gastrointestinal endoscopy (UGE). Seventeen patients with OA (9F/2M; age: 57.47 +/- 9.82 yrs) who did not take NSAIDs were included as a control group. A scale ranging from 0 to 2 (0 = no lesions, 1-minor = red spots or petechiae, denuded areas and/or 1-5 mucosal breaks; 2-major = > 5 mucosal breaks and/or strictures, or hemorrhage) was designed to assess the severity of small bowel mucosal injuries. RESULTS: CE found intestinal lesions in 75% (12/16) of patients in the study group and in 11.76% (2/17) of controls (p < 0.01). Seven out of 16 NSAID consumers (43.75%) and none in the control group (0%) had a major small bowel mucosal injury (p < 0.01). The percentages of patients with grade 1 and 2 gastroduodenopathy in the study group, as assessed by UGE, were 37.14 and 23.81%, respectively. There was no significant difference in the rate of major enteropathy between patients with none or minor gastroduodenal injury, and those with major gastroduodenopathy (43.75 vs. 40%; p = N.S.). CONCLUSIONS: Chronic NSAID intake is associated with a high rate of small bowel mucosal injuries. Our data have failed to demonstrate a relationship between the severity of gastroduodenal and intestinal injury.

Anti-HLA Antibodies After Precocious Transplantectomy by Vascular Thrombosis.

BACKGROUND: Our objective in this study was to determine the effects of early renal transplantectomy on patients and the production of anti-human leukocyte antigen (anti-HLA) antibodies. METHODS: Between January 2003 and May 2017, we analyzed a group of patients for the presence of specific HLA class I and/or II donor-specific antibodies (DSA), their panel-reactive antibodies (PRA), and the time period in which the antibodies were still detectable after transplantectomy. RESULTS: Anti-HLA antibodies were detected in 60.8% of patients, 60.8% and 52.2% of those patients had anti-class I and anti-class II antibodies, respectively. DSA were detected in 91.7% of the anti-HLA class I patients. Class II DSA were detected all of the patients with anti-HLA class II antibodies. The average (mean ± SD) PRA levels in our patients after transplantectomy was 60 ± 34% in class I and 63 ± 36% in class II. CONCLUSION: Anti-HLA antibodies can be detected well after transplantectomy. Even if the kidney allograft had been transplanted for only a short time, when the intensity of immunosuppression was the highest, many patients developed anti-HLA antibodies. The patients who continued with immunosuppression after transplantectomy did not develop anti-HLA antibodies.

Peritubular dentin lacks piezoelectricity.

Dentin is a mesenchymal tissue, and, as such, is based on a collagenous matrix that is reinforced by apatite mineral. Collagen fibrils show piezoelectricity, a phenomenon that is used by piezoresponse force microscopy (PFM) to obtain high-resolution images. We applied PFM to image human dentin with 10-nm resolution, and to test the hypothesis that zones of piezoactivity, indicating the presence of collagen fibrils, can be distinguished in dentin. Piezoelectricity was observed by PFM in the dentin intertubular matrix, while the peritubular dentin remained without response. High-resolution imaging of chemically treated intertubular dentin attributed the piezoelectric effect to individual collagen fibrils that differed in the signal strength, depending on the fibril orientation. This study supports the hypothesis that peritubular dentin is a non-collagenous tissue and is thus an exception among mineralized tissues that derive from the mesenchyme.

Spatial resolution, information limit, and contrast transfer in piezoresponse force microscopy.

Scanning probe-based ferroelectric domain imaging and patterning has attracted broad attention for use in the characterization of ferroelectric materials, ultrahigh density data storage, and nanofabrication. The viability of these applications is limited by the minimal domain size that can be fabricated and reliably detected by scanning probe microscopy. Here, the contrast transfer mechanism in piezoresponse force microscopy (PFM) of ferroelectric materials is analysed in detail. A consistent definition of resolution is developed both for the writing and the imaging processes, and the concept of an information limit in PFM is established. Experimental determination of the object transfer function and the subsequent reconstruction of an 'ideal image' is demonstrated. This contrast transfer theory provides a quantitative basis for image interpretation and allows for the comparison of different instruments in PFM. It is shown that experimentally observed domain sizes can be limited by the resolution of the scanning probe microscope to the order of tens of nanometres even though smaller domains, of the order of several nanometres, can be created.

Bioelectromechanical imaging by scanning probe microscopy: Galvani's experiment at the nanoscale.

Since the discovery in the late 18th century of electrically induced mechanical response in muscle tissue, coupling between electrical and mechanical phenomena has been shown to be a near-universal feature of biological systems. Here, we employ scanning probe microscopy (SPM) to measure the sub-Angstrom mechanical response of a biological system induced by an electric bias applied to a conductive SPM tip. Visualization of the spiral shape and orientation of protein fibrils with 5 nm spatial resolution in a human tooth and chitin molecular bundle orientation in a butterfly wing is demonstrated. In particular, the applicability of SPM-based techniques for the determination of molecular orientation is discussed.

Diagnostic yield of 335 push video-enteroscopies.

BACKGROUND AND OBJECTIVES: The diagnostic yield of push enteroscopy (PE) varies widely from 13 to 78% of cases, according to the various series. The aim of this retrospective cohort study was to determine the endoscopic and histological yield of PE in our health area. PATIENTS AND METHODS: A total of 355 consecutive patients (190 males/165 females; mean age 45 years, range 15-89) underwent PE over a 6-year period, from 1997 to 2003. PE was performed under sedation and without overtube. Small-bowel mucosa biopsies were taken in 199 explorations (56%). Clinical indications for PE included: chronic diarrhea (35%), occult digestive bleeding (ODB) or iron-deficiency anemia (28%), suspected small-bowel malignancy (16%), chronic abdominal pain (28/355; 8%), follow-up of polyposis or malabsorption syndromes (7%), and abnormal radiographic findings (6%). RESULTS: PE detected lesions in 122 cases (34%); in 6 cases (6%) lesions were within the reach of esophagogastroduodenoscopy. A normal macroscopic appearance of the small intestinal mucosa with an abnormal histological study was seen in 16 patients (6%). Major findings included: malabsorptive diseases (14%), nonspecific enteropathy (5%), angiodysplasia (3,5%), lymphangiectasia (3%); jejunal polyps (2%), Crohn s disease (2%), intestinal tumors (2%), extrinsic jejunal strictures (0.5%), and other (10/355; 3%). Abnormal radiographic findings (62%), chronic diarrhea (37%) and ODB (31%) were the indications with a higher diagnostic yield. No major complications were seen. CONCLUSIONS: According to our experience, PE is a safe and useful tool for the evaluation of small-bowel disease, especially in some indications (abnormal radiographic findings, chronic diarrhea, and ODB). Small-bowel biopsy increases PE's diagnostic yield in patients with chronic diarrhea.

Optimised empiric triple and concomitant therapy for Helicobacter pylori eradication in clinical practice: the OPTRICON study.

BACKGROUND: Empiric triple therapy for Helicobacter pylori should be abandoned when clarithromycin resistance rate is >15-20%. Optimisation of triple therapy (high-dose acid suppression and 14-day duration) can increase eradication rates by 10%. AIM: To compare the efficacy and safety of optimised triple (OPT-TRI) and nonbismuth quadruple concomitant (OPT-CON) therapies. METHODS: Prospective multicentre study in 16 Spanish centres using triple therapy in clinical practice. In a 3-month two-phase fashion, the first 402 patients received an OPT-TRI therapy [esomeprazole (40 mg b.d.), amoxicillin (1 g b.d) and clarithromycin (500 mg b.d) for 14 days] and the last 375 patients an OPT-CON treatment [OPT-TRI therapy plus metronidazole (500 mg b.d)]. RESULTS: Seven-hundred seventy-seven consecutive patients were included (402 OPT-TRI, 375 OPT-CON). The OPT-CON therapy achieved significantly higher eradication rates in the per-protocol [82.3% (95% CI = 78-86%) vs. 93.8% (91-96%), P < 0.001] and intention-to-treat analysis [81.3% (78-86%) vs. 90.4% (87-93%), P < 0.001]. Adverse events (97% mild/moderate) were significantly more common with OPT-CON therapy (39% vs. 47%, P = 0.016), but full compliance with therapy was similar between groups (94% vs. 92%, P = 0.4). OPT-CON therapy was the only significant predictor of successful eradication (odds ratio, 2.24; 95% CI: 1.48-3.51, P < 0.001). The rate of participating centres achieving cure rates ≥ 90% favoured OPT-CON therapy (OPT-TRI 25% vs. OPT-CON 62%). CONCLUSIONS: Empiric OPT-CON therapy achieved significantly higher cure rates (>90%) compared to OPT-TRI therapy. Addition of metronidazole to OPT-TRI therapy increased eradication rates by 10%, resulting in more mild adverse effects, but without impairing compliance with therapy.

Salmonella dublin infection: a rare cause of spontaneous bacterial peritonitis and chronic colitis in alcoholic liver cirrhosis.

Salmonella dublin is a veterinary pathogen which rarely causes human illness, although reported human isolates have increased over the past two decades. This serovar of salmonella is unusually invasive and life-threatening, although the clinical pattern of human infection is not well known. We describe a 51-year-old cirrhotic patient who presented with severe liver failure, chronic diarrhoea and left-sided segmental colitis. Radiological and endoscopic findings suggested Crohn's colitis. During the hospital stay he developed a spontaneous bacterial peritonitis (SBP) and S. dublin was isolated in the ascitic fluid. Our report supports the view that this salmonella serovar should be kept in mind as a rare cause of SBP in cirrhotic patients, especially in those cases with chronic colitis resembling Crohn's disease.

Measuring colonic transit time in chronic idiophatic constipation.

INTRODUCTION AND OBJECTIVES: Colonic transit time can define three types of delay: right colon (colonic inertial), left colon and recto sigmoid. The aim of this study is to compare clinic characteristics and manometric results among the different groups with segmental colonic transit disorder. PATIENTS AND METHODS: 61 subjects were included in our study (5 men and 56 women) with and average age of 47.5 years (range: 17-84 years). We carried our a study of segmental and total colonic transit time, with the use of radio-opaque markers and sequential abdominal X-rays. We considered that transit time was prolonged when it was longer than 72 hours, and segmental transit time, when right colon was longer than 22 hours, left colon 37.2 hours and recto-sigmoid 37.2 hours. We included different clinic data: age, sex, place of residence stool frequency, abdominal pain, painful evacuation, incomplete evacuation, evacuation desire, dietary fibre intake, use of laxatives. We practised anorectal manometry in 20 patients. RESULTS: The average total colonic transit time was 38.2 hours in normal transit and 103 hours with disorder. The frequency in the three colonic segments, when there was a long total colonic transit time, was: 40% in the left colon, 33% in the recto-sigmoid and 27% in the right colon. We analysed the clinical characteristics of these three groups, finding more frequency of painful evacuation and defecation desire and lower dietary fibre intake in recto sigmoid. The most important abnormality in anorectal manometry was the hiposensitivity in the anorectal area, that only appeared in subjects with long segmental transit time in the right colon (colonic inertia), statistically significant. CONCLUSIONS: The measurement of colonic transit time with radio-opaque markers is a simple technique that allows for the objective detection of the different groups of patients with chronic idiopathic constipation. The exact typification of the abnormality is important for the individualization of each treatment.

Incidence and factors influencing on Helicobacter pylori infection recurrence.

OBJECTIVES: a) To determine the rate of H. pylori reinfection after successful eradication in a 4-year follow-up study; and b) To evaluate the contribution of different factors in the infection relapse. PATIENTS AND METHODS: A total of 208 patients (age range 18-81 years; average 50 years; 87 women) who had been successfully treated for H. pylori infection were included. Annually, urea breath test was assessed to determine H. pylori status after eradication. Age, sex, rural/urban environment, smoking habit, treatment regimens against H. pylori and urea breath test values were evaluated. RESULTS: reinfection occurred in 9,6% of patients observed, 6,7% (14/208) in the first year, 1,9% (4/208) in the second year, 1% (2/208) in the third and 0% in the forth. Risk factors for infection recurrence were younger age and higher values of urea breath test in the multivariante analysis. CONCLUSIONS: annual reinfection rate was 2,4 pacients-year. Younger patients and higher values of urea breath test were factors associated with a higher rate of reinfection relapse. Annually, urea breath test should be performed to detect reinfection in order to avoid ulcer complications.

[Non-steroidal anti-inflammatory drugs and cyclooxygenase-2 selectivity in gastroenterology]. / Los antiinflamatorios no esteroideos y selectividad sobre la ciclooxigenasa tipo II en Gastroenterología.

The discovery of, at least, two isoforms of the enzyme cyclooxygenase, named by the numbers 1 and 2, has updated our knowledge about the NSAID. This has led investigators to reconsider what we can expect from this kind of drugs. The two isoforms share enzymatic and structural properties, although they are regulated differently, at molecular level and can be distinguished from their functions, although an overlap of roles between them do exist. The main goal of the development of highly selective inhibitors is to improve gastric tolerability. The classical NSAID inhibit preferentially the isoform 1 of the cyclooxygenase, in vitro, which appears to be dangerous, according to gastrointestinal safety profile. The new compounds with high selectivity for the isoform 2 of the cyclooxygenase could be better tolerated at gastrointestinal level. Meanwhile these compounds also could have a potential use in several diseases such as colorectal cancer and neurodegenerative processes. The potential occurrence of side effects, perhaps related with renal function, should be noted. Finally large controlled clinical trials are needed to estimate the therapeutic advantages which can be offered by the new highly selective NSAID, and the potential consequences which can result from the isoform 2 of the cyclooxygenase prolonged inhibition

Usefulness of capsule endoscopy in patients with suspected small bowel disease.

AIM: To study the usefulness and safety of capsule endoscopy as a diagnostic tool in various small bowel disorders. DESIGN: A retrospective analysis of a series of cases. MATERIAL AND METHODS: Between August 2001 and August 2002, 92 capsule endoscopy procedures were performed in 88 patients (53M/39F, age: 43.87 +/- 16.78). Indications included: chronic diarrhea (n=33); unknown abdominal pain (n=29); occult gastrointestinal bleeding or iron-deficiency anemia (n=13); abdominal discomfort in NSAID takers (n=7); staging of gastrointestinal tumors (n=4), and asymptomatic controls (n=2). Previously performed gastroscopy, colonoscopy, and small-bowel follow-through were not conclusive in all patients. RESULTS: Most frequently relevant findings included: jejuno-ileal aphtas and ulcerations (29 patients), vascular malformations (13 patients), and intestinal neoplasm (6 patients). The groups with a higher rate of findings related to this indication were occult gastrointestinal bleeding (76.92%) and chronic diarrhea (67.85%), with the lowest rate in the abdominal pain group (34.48%). Therapeutic strategy was directly changed in 36 of 88 patients (40.90%) because of capsule-endoscopic findings. The only observed complication was the failed excretion of one of the capsules because of an unknown ulcerated intestinal stricture. CONCLUSIONS: Capsule endoscopy is a safe procedure which can study the entire small bowel, meaning a valuable tool for the management of patients with suggestive signs and symptoms of intestinal disorders.

Piezoelectric properties of aligned collagen membranes.

Electromechanical coupling, a phenomenon present in collagenous materials, may influence cell-extracellular matrix interactions. Here, electromechanical coupling has been investigated via piezoresponse force microscopy in transparent and opaque membranes consisting of helical-like arrays of aligned type I collagen fibrils self-assembled from acidic solution. Using atomic force microscopy, the transparent membrane was determined to contain fibrils having an average diameter of 76 ± 14 nm, whereas the opaque membrane comprised fibrils with an average diameter of 391 ± 99 nm. As the acidity of the membranes must be neutralized before they can serve as cell culture substrates, the structure and piezoelectric properties of the membranes were measured under ambient conditions before and after the neutralization process. A crimp structure (1.59 ± 0.37 µm in width) perpendicular to the fibril alignment became apparent in the transparent membrane when the pH was adjusted from acidic (pH = 2.5) to neutral (pH = 7) conditions. In addition, a 1.35-fold increase was observed in the amplitude of the shear piezoelectricity of the transparent membrane. The structure and piezoelectric properties of the opaque membrane were not significantly affected by the neutralization process. The results highlight the presence of an additional translational order in the transparent membrane in the direction perpendicular to the fibril alignment. The piezoelectric response of both membrane types was found to be an order of magnitude lower than that of collagen fibrils in rat tail tendon. This reduced response is attributed to less-ordered molecular assembly than is present in D-periodic collagen fibrils, as evidenced by the absence of D-periodicity in the membranes.

Electromechanical properties of dried tendon and isoelectrically focused collagen hydrogels.

Assembling artificial collagenous tissues with structural, functional, and mechanical properties which mimic natural tissues is of vital importance for many tissue engineering applications. While the electro-mechanical properties of collagen are thought to play a role in, for example, bone formation and remodeling, this functional property has not been adequately addressed in engineered tissues. Here the electro-mechanical properties of rat tail tendon are compared with those of dried isoelectrically focused collagen hydrogels using piezoresponse force microscopy under ambient conditions. In both the natural tissue and the engineered hydrogel D-periodic type I collagen fibrils are observed, which exhibit shear piezoelectricity. While both tissues also exhibit fibrils with parallel orientations, Fourier transform analysis has revealed that the degree of parallel alignment of the fibrils in the tendon is three times that of the dried hydrogel. The results obtained demonstrate that isoelectrically focused collagen has similar structural and electro-mechanical properties to that of tendon, which is relevant for tissue engineering applications.