Defined morphological criteria allow reliable diagnosis of colorectal serrated polyps and predict polyp genetics

Criteria for the diagnosis of serrated colorectal lesions (hyperplastic polyp, sessile serrated adenoma without or with dysplasia—which we called mixed polyp—and traditional serrated adenoma) for which consensus has been reached should be validated for applicability in daily practice in terms of inter-observer reproducibility and their association with clinical features and (epi)genetic events. A study set was created from a consecutive series of colorectal polyps (n?=?1,926) by selecting all sessile serrated adenomas, traditional serrated adenomas and mixed polyps. We added consecutive series of hyperplastic polyps, classical adenomas and normal mucosa samples for a total of 200 specimens. With this series, we conducted an inter-observer study, encompassing ten pathologists with gastrointestinal pathology experience from five European countries, in three rounds in which all cases were microscopically evaluated. An assessment of single morphological criteria was included, and these were correlated with clinical parameters and the mutation status of KRAS, BRAF and PIK3CA and the methylation status of MLH1. Gender, age and localisation were significantly associated with certain types of lesions. Kappa statistics revealed moderate to good inter-observer agreement for polyp classification (κ = 0.56 to 0.63), but for single criteria, this varied considerably (κ = 0.06 to 0.82). BRAF mutations were frequently found in hyperplastic polyps (86 %, 62/72) and sessile serrated adenomas (80 %, 41/51). KRAS mutations occurred more frequently in traditional serrated adenomas (78 %, 7/9) and less so in classical adenomas (20 %, 10/51). Single morphological criteria for sessile serrated adenomas showed significant correlation with BRAF mutation (all p?≤?0.001), and those for classical adenomas or traditional serrated adenoma correlated significantly with KRAS mutation (all p?<?0.001). Therefore, single well-defined morphological criteria are predictive for genetic alterations in colorectal polyps.     

Synthesis and photophysical studies of self-assembled multicomponent supramolecular coordination prisms bearing porphyrin faces

Multicomponent self-assembly, wherein two unique donor precursors are combined with a single metal acceptor instead of the more common two-component assembly, can be achieved by selecting Lewis-basic sites and metal nodes that select for heteroligated coordination spheres. Platinum(II) ions show a thermodynamic preference for mixed pyridyl/carboxylate coordination environments and are thus suitable for such designs. The use of three or more unique building blocks increases the structural complexity of supramolecules. Herein, we describe the synthesis and characterization of rectangular prismatic supramolecular coordination complexes (SCCs) with two faces occupied by porphyrin molecules, motivated by the search for new multichromophore complexes with promising light-harvesting properties. These prisms are obtained from the self-assembly of a 90° Pt(II) acceptor with a meso-substituted tetrapyridylporphyrin (TPyP) and dicarboxylate ligands. The generality of this self-assembly reaction is demonstrated using five dicarboxylate ligands, two based on a rigid central phenyl ring and three alkyl-spaced variants, to form a total of five free-base and five Zn-metallated porphyrin prisms. All 10 SCCs are characterized by ³¹P and ¹H multinuclear NMR spectroscopy and electrospray ionization mass spectrometry, confirming the structure of each self-assembly and the stoichiometry of formation. The photophysical properties of the resulting SCCs were investigated revealing that the absorption and emission properties of the free-base and metallated porphyrin prisms preserve the spectral features associated with free TPyP.The use of sunlight is ubiquitous as the input for carbon-neutral, renewable energy schemes (1). Every strategy that relies on solar energy conversion, ranging from direct conversion to electricity in photovoltaics (2) to the generation of fuels via electrocatalysis (3), photoanode (4, 5), or photocathode devices (6), or photocatalysis (7) requires that photons be absorbed by a molecule or material as the first step in providing the driving force for subsequent transformation. Natural systems have evolved light-harvesting complexes, comprising multiprotein ensembles embedded with pigment molecules to enhance photon absorption for photosynthesis (8). These pigment-rich sites are arranged such that excitation of a distal chromophore will ultimately result in energy transfer to a reaction center via a series of migration and transfer processes (9). Strategies to replicate natural light-harvesting complexes necessarily demand the organization of multiple chromophores (10), a requirement that makes self-assembly and supramolecular chemistry particularly well suited for such efforts (11–13). As such, a variety of approaches have been applied toward the development of new materials that exhibit broadband absorption and efficient energy transfer (14–16). The subsequent studies of such materials span investigations of the fundamental science behind energy migration and transfer, to practical applications in devices.Many of these designs incorporate porphyrin-based molecules (17–22), a pigment that is related to the ubiquitous chlorophyll found in natural light-harvesting systems (23). Porphyrins possess characteristic structural and photophysical properties that make them well suited for adaptation into artificial designs, not only for solar energy conversion but also for applications in photodynamic therapy (24–29), enzyme mimics (30–32), catalysis (33–37), and molecular electronic devices (38, 39). In the context of solar energy, many multiporphyrin light-harvesting designs have been developed ranging from organic polymers, metal-organic frameworks, and supramolecular ensembles. Porphyrins are remarkable precursors for incorporation into supramolecular designs due to their established syntheses that facilitate well-defined functionalization, the commercial availability of simple variants, and their ability to accommodate a wide range of metal ions, thus unlocking suites of complexes for a given design (40, 41). The absorption spectra of porphyrin molecules are dominated by so-called Soret bands in the 380- to 500-nm range, accompanied by a set of weaker, but still considerably intense Q bands in the 500- to 700-nm range. Because these bands result in the absorption of visible photons, the attractiveness of porphyrins in solar conversion schemes becomes apparent. Furthermore, the emission wavelengths of a given porphyrin may align with its Q-band absorption, providing the spectral overlap that is required for efficient energy migration.Although extended structures such as polymers and metal-organic frameworks can organize similar numbers of pigments as are found in natural systems (42–47), their study can be complemented by relatively smaller supramolecules that facilitate characterization and study, preserving attractive properties such as solubility and facile tenability (48, 49). As such, coordination-driven self-assembly has been used to explore porphyrin-based supramolecular coordination complexes in traditional one- or two-component schemes (50-53).The recent development of new strategies for multicomponent self-assembly has provided a method to increase the structural complexity of chromophoric supramolecular coordination complexes (SCCs) wherein three or more building blocks can assemble into a single thermodynamically favored product (54, 55). One method to achieve multicomponent assembly is to identify metal nodes and ligands that prefer heteroligated coordination spheres, thus avoiding statistical mixtures of products. For example, when Pt(II) ions are combined with pyridyl and carboxylate-based ligands, mixed Pt-N,O coordination environments are formed exclusively (56). This method has been used recently to construct a variety of 2D and 3D SCCs and also provides the basis for supramolecule-to-supramolecule transformation, wherein a Pt-pyridyl SCC may be mixed in the proper stoichiometry with a Pt-carboxylate SCC to quantitatively furnish a third multicomponent SCC (56). Furthermore, traditional two-component assembly typically requires the use of rigid building blocks so as to maintain the angularity and directionality that determines the structural outcome of a reaction. In contrast, multicomponent approaches also permit the use of structurally ambiguous ligands, provided the remaining building blocks enforce a proper degree of directionality. As such, alkyl-based building blocks may be used in such self-assembly schemes, despite the fact that rotation about the carbon–carbon bonds means that a single orientation of the coordination vectors is not maintained (57).We report here a unification of many recent themes of coordination-driven self-assembly: the formation of multichromophore complexes as motivated by the need for new light-harvesting materials, multicomponent self assembly using Pt(II) heteroligation, and alkyl-based dicarboxylates in the formation of 3D prisms that demonstrate a hitherto-underexplored class of building blocks for coordination-driven self-assembly. The synthesis and characterization of a suite of 10 prisms is described, thus demonstrating the structural modularity and tunability that is possible through self-assembly approaches. Five prisms are formed containing free-based tetrapyridyl porphyrin, with the remaining five being their Zn-containing analogs. The absorption and emission properties of the SCCs are evaluated and compared with free tetrapyridylporphyrin (TPyP) revealing that, upon incorporation into prisms, the photophysical properties remain largely unchanged. In addition, the solubility of the prisms far exceeds that of the parent TPyP, indicating that coordination-driven self-assembly may be a powerful method to optimize the physiochemical characteristics of new light-harvesting materials.     

The ameliorating effect of Rosa roxburghii against ethanol-induced psychomotor alterations in rats

Background: Ethanol (EtOH) is one of the oldest recreational substances known to man, primarily taken because it induces a sense of well-being (euphoric effects) and relaxation (anxiolytic effects). EtOH use entails various negative consequences. Of particular interest are EtOH-induced psychomotor alterations, because of its immediate manifestation and adverse consequences. Rosa roxburghii (RR), a wild plant of Southwest China, has gained attention on account of its numerous beneficial effects on the immune, nervous, and cardiovascular systems. Objective: In the present study we assessed the effects of Rosa roxburghii (RR) on EtOH-induced psychomotor alterations in rats. Methods: Sprague Dawley rats were orally administered distilled water (control group) or ethanol (4?g/kg BW) (EtOH-group) to induce psychomotor alterations. RR extract (25, 50, and 100?mg/kg, p.o.) was administered 30?min before EtOH treatment (RR-group). EtOH-induced psychomotor alterations were evaluated in the open-field, accelerating rotarod, hanging wire, and cold swimming tests. Behavioral evaluation and hematological analysis (EtOH and acetaldehyde concentration) were done at 1, 2, 4 and 8 hours after EtOH administration. Results: The EtOH group showed psychomotor alterations as compared with the control group. These EtOH-induced psychomotor alterations were directly related to the rise in blood ethanol and acetaldehyde concentrations. Pre-treatment of RR significantly improved EtOH-induced psychomotor alterations on open-field, accelerating rotarod, hanging wire, and cold swimming tests. These improvements in psychomotor performance coincided with the decreased blood ethanol and acetaldehyde levels observed in the RR-treated group. Conclusion: These results suggest that RR has ameliorating effects against EtOH-induced psychomotor alterations.     

Echocardiographic evolution of pulmonary artery pressure after acute pulmonary embolism. Results from IPER registry

Aims

The aim of the study is to describe the course of the echocardiographically measured pulmonary artery systolic pressure (PAsP) in a series of patients included in the Italian Pulmonary Embolism Registry (IPER).

Methods

Patients with confirmed PE received an echo-Doppler evaluation within 24 hours from hospital admission and after one year. Pulmonary hypertension (PH) was considered “likely” , “possible” or “unlikely” with a right ventricular-right atrial (RV-RA) pressure gradient > 45 mm Hg, between 32 and 45 mm Hg and ≤ 31 mm Hg and no additional echocardiographic variables suggestive of PH, respectively.

Results

We studied 286 patients (169 females and 117 males, mean age 67 ± 15; mean follow-up 387 ± 45 days): 240 had a baseline tricuspid regurgitation (TR) and a RV-RA gradient of variable degree. PH was considered likely, unlikely and possible in 97, 93 and 50 patients respectively. At FU echocardiography, 6 patients (2.1%) had a likely PH and all of them were part of the group of 97 patients with a baseline likely PH; 24 patients (8.4%) had a possible PH, and 67% of them had an initial likely PH. No patients with a baseline unlikely PH or without TR developed a follow-up PH (both likely or possible). The probability to show a likely PH at FU echocardiography for patients with a baseline RV-RA gradient > 45 mm Hg was 6.2%, while the probability not to have a likely PH for patients with a baseline RV-RA gradient ≤ 45 mm Hg was 100%.

Conclusion

In our study population of patients with acute PE, we observed that those presenting with a baseline echocardiographic RV-RA pressure gradient ≤ 45 mm Hg were completely free from a likely PH after 1-year.     

Can premenstrual syndrome affect arterial stiffness or blood pressure?

ObjectiveWe tested the hypotheses that monthly fluctuations in markers of arterial stiffness and blood pressure hemodynamics differ between women with and without premenstrual syndrome. We also assessed hypertension prevalence and arterial stiffening in postmenopausal women with or without history of premenstrual symptoms.MethodsTwenty one pre-menopausal women with premenstrual syndrome and 15 women without were prospectively examined in three distinct phases of their menstrual cycle (menses, late follicular and luteal phase). Pulse-wave velocity and analysis were used to assess arterial stiffness and wave reflection indices, respectively. Endothelial function was evaluated by flow-mediated vasodilation. In a cross-sectional substudy, 156 postmenopausal women were assessed for possible associations between retrospectively reported PMS symptoms and hypertension.ResultsIn women with premenstrual syndrome, arterial stiffness significantly increased during the luteal and menses phase (late follicular: 6.48 ± 1.07, luteal: 7.1 ± 1.26, menstruation: 7.12 ± 1.19 m/s, p = 0.003), while blood pressure peaked at the menses phase. Significant interactions between PMS and changes in arterial stiffness and blood pressure but not endothelial function, were observed. Changes in PWV were significantly associated with concomitant changes in blood pressure, C-reactive protein and the severity of PMS symptoms. The prevalence of hypertension (20.9% vs. 40.9%, p = 0.041) and pulse-wave velocity values (8.64 ± 1.52 vs. 9.37 ± 1.1, p = 0.046) were higher in postmenopausal women with 7 or more reported PMS symptoms. Arterial stiffness differences remained significant after adjustment for confounding factors.ConclusionThese results imply that PMS may affect arterial stiffness and BP monthly variability. Whether PMS is associated with new onset hypertension later in life needs further evaluation.