Pacinian Corpuscles as a Diagnostic Clue of Ledderhose Disease-A Case Report and Mapping of Pacinian Corpuscles of the Sole.

BACKGROUND: Plantar fibromatosis, known as Ledderhose disease, is a neoplastic disease characterized by a locally-aggressive bland fibroblastic proliferation. Although Pacinian corpuscles alterations are commonly described in palmar fibromatosis, there are still no references about Pacinian corpuscles alterations in the rarer plantar version. METHODS: We present a case report where a wide cutaneous resection, including the plantar fascia was performed, allowing a detailed study of Pacinian corpuscles. Pacinian corpuscles were analyzed using immunohistochemistry for neurofilament proteins, S100 protein, CD34, vimentin, glucose transporter 1, epithelial membrane antigen, neural-cell adhesion molecule, actin, desmin, type IV collagen, and high-affinity neurotrophin Trk-receptors. Moreover, the density and the size of the corpuscles were determined. RESULTS: A clear increase in the number (hyperplasia) of Pacinian corpuscles was evidenced in the Ledderhose disease plantar fascia in comparison with similarly aged normal subjects. Pacinian hypertrophy was not demonstrated, but a significant decrease in the number of corpuscular lamellae was noted, with a subsequent increase in the interlamellar spaces. Pacinian corpuscles from the pathological plantar fascia showed an abnormal structure and immunohistochemical profile, generally without identifiable axons, and also absence of an inner core or an intermediate layer. Moreover, other molecules related with trophic maintenance of corpuscles were also absent. Finally, a vascular proliferation was commonly noted in some corpuscles, which involved all corpuscular constituents. CONCLUSION: The observed Pacinian corpuscles hyperplasia could be considered a diagnostic clue of plantar fibromatosis.

Endoscopic ultrasound-guided fine-needle biopsy in patients with unexplained diffuse gastrointestinal wall thickening.

Background and study aims Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is recommended after non-diagnostic biopsy in gastrointestinal wall thickening, although the performance of currently available FNB needles in this setting is unknown. We aimed to assess the diagnostic accuracy and safety of EUS-FNB and to evaluate the "T" wall staging in malignant pathology. Patients and methods This was a single center retrospective study that included all consecutive patients undergoing EUS-FNB for diffuse gastrointestinal wall thickening with at least one previous negative conventional endoscopic biopsy between January 2016 and November 2019. EUS-FNB was performed using linear-array echoendoscopes with slow-pull/fanning technique. Tissue acquisition was done with 19- or 22-gauge biopsy needles. Samples were included in formalin without rapid on-site evaluation and submitted for histopathological processing. The final diagnosis was based on conclusive histology or absence of evidence of disease progression after follow-up at least 6 months. Results Twenty-nine patients (21 men), with a median age of 68 (IQR: 56-77), were included. EUS-FNB was technically feasible and the sample quality was adequate for full histological assessment in all patients (100 %). Sensitivity, specificity, positive and negative predictive values, and overall accuracy for diagnosis of malignancy were 95.5 %, 100 %, 100 %, 83.3 %, and 96.3 %, respectively. In patients with malignant disease, the samples obtained allowed detection of signs of deep layer infiltration ("histological staging") in 17 of 21 cases (81 %). No adverse events were noted. Conclusions The EUS-FNB technique demonstrated excellent diagnostic performance and safety in the study of unexplained diffuse gastrointestinal wall thickening. Histological staging was obtained in a high percentage of samples.

Patency of endoscopic ultrasound-guided gastroenterostomy in the treatment of malignant gastric outlet obstruction.

Background and study aims Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) with a lumen-apposing metal stent (LAMS) is a novel, minimally invasive technique in the palliative treatment of malignant gastric outlet obstruction (GOO). Several studies have demonstrated feasibility and safety of EUS-GE, but evidence on long-term durability is limited. The aim of this study was to evaluate patency of EUS-GE in treatment of malignant GOO. Patients and Methods An international multicenter study was performed in seven centers in four European countries. Patients who underwent EUS-GE with a LAMS between March 2015 and March 2019 for palliative treatment of symptomatic malignant GOO were included retrospectively. Our main outcome was recurrent obstruction due to LAMS dysfunction; other outcomes of interest were technical success, clinical success, adverse events (AEs), and survival. Results A total of 45 patients (mean age 69.9 ±â€Š12.3 years and 48.9 % male) were included. Median duration of follow-up was 59 days (interquartile range [IQR] 41-128). Recurrent obstruction occurred in two patients (6.1 %), after 33 and 283 days of follow-up. Technical success was achieved in 39 patients (86.7 %). Clinical success was achieved in 33 patients (73.3 %). AEs occurred in 12 patients (26.7 %), of which five were fatal. Median overall survival was 57 days (IQR 32-114). Conclusions EUS-GE showed a low rate of recurrent obstruction. The relatively high number of fatal AEs underscores the importance of careful implementation of EUS-GE in clinical practice.

CISNE: An accurate description of dose-effect and synergism in combination therapies.

The precise determination of dose-effect curves and the combination effect of drugs is of crucial importance in the development of new therapies for the most dreadful diseases. We have found that the current implementations of the theory of Chou et al. are not accurate enough in some circumstances and might lead to erroneous predictions of synergistic or antagonistic behaviour. We have identified the source of inaccuracies and fixed it thereby improving the accuracy of those methods. Here we explain the main features of our approach and demonstrate its higher accuracy as compared to the standard methods. Therefore, this new implementation might have a huge impact in the reliability of future research on new Combination Therapies.

Evaluation of the Quality of Semen and Sexual Function in Men with Inflammatory Bowel Disease.

BACKGROUND: Data on fertility rates and medication safety in men with inflammatory bowel disease (IBD) are limited. The aim of this study was to evaluate whether there is a seminal alteration in patients with IBD and, if so, to evaluate the mechanisms that may play a role according to what has been described in the literature. Its secondary aim was to evaluate the impact on male sexual function of IBD. METHODS: Multicenter, cross-sectional, case series study comparing men with IBD and control subjects. Semen analysis was performed according to the recommendations of World Health Organization. The impact on male sexual function was evaluated with the International Index of Erectile Function questionnaire. RESULTS: On multivariate analysis, patients with Crohn's disease had lower sperm concentrations compared with those with ulcerative colitis (median [interquartile range], 34.5 [19.2-48] versus 70 [34.5-127.5], P = 0.02) and lower seminal zinc levels (mean ± SD, 1475 ± 235 µmol/L versus 2221 ± 1123 µmol/L, P = 0.04). Patients with Crohn's disease on anti-tumor necrosis factor treatment had better progressive motility (mean ± SD, 56.7 ± 17.7 versus 35.1 ± 22.1, P = 0.01) and sperm morphology (14.4 ± 7.1 versus 7.6 ± 4.9, P = 0.04) than those who were not on anti-tumor necrosis factor. Regarding sexual function, no significant differences were found across patients with IBD and control subjects. CONCLUSIONS: Men with Crohn's disease showed a trend toward poorer semen quality than those with ulcerative colitis. Treatment with anti-tumor necrosis factor drugs does not seem to be associated with poor sperm quality. In patients in clinical remission, male sexual function is not affected by IBD.

Sequential incorporation of metallic cations (Cd2+ and Hg2+) and N-octylamine into titanium phosphate nanoparticles and their subsequent release in acid media.

Titanium phosphate nanoparticles, TPNP, consisting of a NaTi2(PO4)3 core and a shell of hydrogen phosphate and dihydrogen phosphate of titanium, undergo fast hydrolysis in water releasing phosphoric acid. This reaction is inhibited in the presence of metallic ions like Cd2+ or Hg2+, which are able to replace the protons of the shell acid phosphates. The amount of the adsorbed metallic cations could be regulated using counterions of different basicity. The resulting nanoparticles also incorporate NH2(CH2)7CH3 (N-octylamine) at room temperature forming N-octylammonium/phosphate ion pairs, but it was found that at higher cation concentration inside the nanoparticle, a lower amount of amine was adsorbed. The metallic cations and N-octylamine are released in acid media, but the starting material is not fully recovered.

Knowledge acquired, satisfaction attained and attitudes towards shared decision making in colorectal cancer screening.

BACKGROUND: Introducing shared decision making (SDM) in colorectal cancer (CRC) screening requires patients to acquire appropriate knowledge. We aimed to describe the knowledge attained by subjects with a family history of CRC. METHODS: Consecutive patients attending the gastroenterology clinic for a CRC family history were invited to take part in a cross-sectional survey. Attitudes towards SDM, satisfaction with the information received, knowledge currently achieved, and relevant influencing factors were evaluated. Satisfaction and attitudes towards SDM were evaluated with Likert scale questions. Knowledge was surveyed with closed (80%) and open (20%) questions. RESULTS: Of the 160 patients, 42.7% were male and the median age was 51.8 years (interquartile range: 43.9-58.5). Most subjects favored SDM; only 12.8% (8.4-19.1%) favored passive attitudes. Satisfaction with the information received about what a colonoscopy is and why it is recommended was adequate in 83.1% (76.4-88.2%). Information about risks satisfied 62.9% (55-70.1%) and about alternatives to colonoscopy only 30.6% (23.8-38.3%). The benefits of screening were better known than its risks and alternatives. The CRC decrease associated with screening was known to 71.3% (63.7-77.8%), but only 38.5% (31.1-46.4%) knew that a reduced risk still exists. Just 21.2% (15.5-26.9%) could mention an alternative screening method to colonoscopy and only 42.5% (35-50.4%) were aware of any associated harm. On multivariate analysis, higher educational level and younger age of the attending physician were associated with higher knowledge scores. CONCLUSION: SDM is considered favorably by most patients. Although information about the benefits of CRC screening is transmitted adequately, risks and alternatives should be better addressed.

Changes in antioxidant compounds during the shelf life of commercial tomato juices in different packaging materials.

Tomatoes provide an optimal mix of dietary antioxidants that may be responsible for the reported health benefits of tomato consumption. However, technological processing, packaging materials, and storage conditions have an impact on the nutritional quality of tomato products by affecting the stability of antioxidant nutrients to different extents. In this study, we evaluated the stability of the antioxidant compounds (lycopene, ascorbic acid, total phenols, and total flavonoids) present in commercially available tomato juices during storage extended for 12 months at three different temperatures (8, 22, and 37 degrees C). To further characterize the impact of storage conditions, two commonly used packaging materials (Tetra pack and glass bottles) were used to determine whether packaging materials affect antioxidant stability. Overall, the total lycopene, total phenolic compounds, and total flavonoids remained almost stable during storage for 12 months, regardless of the packaging material used, indicating that tomato juices maintain their nutritional value in terms of antioxidant composition during their shelf life. However, ascorbic acid was the most labile antioxidant and was markedly affected by storage conditions. The hydrophilic total antioxidant activity (TAA) paralleled the losses in ascorbic acid content, whereas the lipophilic TAA remained substantially stable throughout the storage trial.

Phenolic-rich juice prevents DNA single-strand breakage and cytotoxicity caused by tert-butylhydroperoxide in U937 cells: the role of iron chelation.

The antioxidant potential of phenolic compounds is generally linked to their ability to scavenge free radicals. However, in addition to their radical-scavenging activity, phenolic compounds can chelate metal ions, such as iron, to prevent their participation in Fenton-type reactions, which lead to the formation of free radicals. The aim of the present study was to evaluate the ability of a phenolic-rich juice made from grapes, cherries and berries to protect human myeloid leukemia (U937) cells from oxidative stress caused by tert-butylhydroperoxide (tB-OOH). Preincubation of cells with extracts of the phenolic-rich juice at different concentrations (0-200 microM ferulic acid equivalents) for 3 h partially prevented cell death and abolished the DNA cleavage induced by tB-OOH. Moreover, when preincubating cells with the 100-microM juice extract (the dose that diminished cell death by around 50%), the partial prevention of tB-OOH-induced formation of reactive oxygen species (ROS) and mitochondrial permeability transition pore opening was observed. The radical scavenger antioxidant N,N'-diphenyl-1,4-phenylene-diamine (DPPD) and the intracellular iron chelator o-phenanthroline (o-Phe) were also tested to know whether protective effects depended on radical-scavenging or iron-chelating activities. o-Phe prevented cell death, DNA cleavage and ROS generation, whereas DPPD only prevented cell death, suggesting that phenolics in the juice afforded protection against induced oxidative stress, most probably by means of an iron-chelating mechanism.

Molecular dynamics (MD) simulations and large-angle X-ray scattering (LAXS) studies of the solid-state structure and assembly of isotactic (R)-poly(2,2'-dioxy-1,1'-binaphthyl-)phosphazene in the bulk state and in the cast film.

The intrachain conformation, molecular structure and interchain assembly of isotactic (R)-poly(2,2'-dioxy-1,1'-binaphthyl)phosphazene (P-DBNP) both in the bulk state (I) and in the cast film (II) were studied by molecular dynamics (MD) simulations of models, as implemented by a bias potential for the analysis of the radial distribution function (RDF) obtained from large-angle X-ray scattering (LAXS) data. The microscopic structure and order extension of the polymer changed from I to II, as qualitatively shown in the shapes of their experimentally measured RDF curves. With the use of a bias potential, the MD simulations provided a much more accurate analysis of the models, as seen in the reproduction of the RDFs. The chiral P-DBNP chain was found to be consistent with helix conformations in both the I and the II samples. The predominant interchain clustering motif was best reproduced with a seven-chain model. In the case of I, the maximum chain length was 18 monomeric -R(2)NP- units, while in the case of the cast film II the chain was more elongated, up to distances of approximately 100 A, equivalent to over 48 monomeric -R(2)NP- units. The seven-chain assembly was accounted for in terms of nonbonded interactions favouring the minimum voids area between the seven tubular structures of the material. The results validate our earlier finding that MD analysis with implementation of a biasing potential for the RDFs can provide quantitative information on the structural and conformational features of amorphous solids. The combined theoretical and experimental approach was found to be a useful tool to detect, locate and evaluate the intra- and intermolecular modifications of materials subsequent to their phase transformation and, as in the present case, changes in their microscopic structures or preparation methods.

Macromolecular polyradicals with cyclic triphosphazene as a core. Spectral and electrochemical properties.

Stable cyclotriphosphazenes 5 and 6, with three and four carbon radical centers, have been prepared by condensation of (4-hydroxy-2,6-dichlorophenyl)bis(2,4,6-trichlorophenyl)methyl radical (4) with tetrachloro-2,2'-dioxybiphenylcyclotriphosphazene (7). EPR studies of both polyradicals in fluid solution suggest an electronic communication through the PN multiple bonds of the cycle. EPR spectral results in frozen solutions and magnetic susceptibility measurements in the solid are consistent with very weak electron-electron dipolar interactions. Reductive cyclic voltammetry shows a single three-electron redox couple for triradical 5 and a single four-electron redox couple for tetraradical 6. Both polyradicals 5 and 6 have been chemically oxidized to a stable trication 5(3+) and a tetracation 6(4+), respectively, by electron-transfer reactions.

A simplified and convenient laboratory-scale preparation of 14N or 15N high molecular weight poly(dichlorophosphazene) directly from PCl5.

A simple and convenient one-pot synthesis of THF solutions of high molecular weight poly(dichlorophosphazene) [NPCl(2)](n), or the (15)N isotopomer [(15)NPCl(2)](n), starting directly from PCl(5) and NH(4)Cl or (15)NH(4)Cl in a solution of 1,2,4-trichlorobenzene in the presence of sulfamic acid and calcium sulfate dihydrate, is described. The solutions of [NPCl(2)](n) in THF, which are obtained free of poly(tetrahydrofuran) by preparing them in the presence of K(2)CO(3), can be reacted directly with phenols, biphenols, or even HO-CH(2)CF(3) in the presence of K(2)CO(3) or Cs(2)CO(3) to obtain, after a very simple workup, the corresponding polyphosphazene derivatives almost free of chlorine.