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Williamson Amstrup posted an update 6 months, 3 weeks ago
An NMR-based screen of a highly curated ~14 000-member fragment library produced 21 fragment leads. Of these, three were selected for elaboration based on structure-activity relationships generated through cycles of structural analysis by X-ray crystallography, structure-guided design principles, and synthetic chemistry. These results, combined with crystal structures of the first linked fragment compounds, demonstrate the applicability of the fragment-based approach to the discovery of RAGE inhibitors.Ethnic-racial background may influence college students’ psychological sense of community (PSOC). Vandetanib in vitro Thus, it is critical to examine whether this construct is conceptualized similarly between non-Hispanic, Black and Hispanic students. This study tested the measurement invariance of the Brief Sense of Community Scale (BSCS) across the two groups. We used data from a self-administered online survey provided to college students in 2016 in a Northeastern urban university (non-Hispanic, Black = 307; Hispanic = 409). We tested the measurement invariance of the BSCS using a series of nested multigroup confirmatory factor analyses with increasingly restrictive sets of parameters. Measurement invariance of the BSCS across non-Hispanic, Black and Hispanic college students was achieved. The BSCS successfully measures the multidimensionality of PSOC across the two groups in a college setting. Students’ score on the BSCS is not biased by measurement invariance related to cultural influences. When using the BSCS, community psychologists and researchers can have confidence that the observed differences in PSOC across non-Hispanic, Black and Hispanic college students are attributable to true differences rather than a cultural understanding of the construct.Micropapillary carcinoma (MPC) is a morphologically distinctive form of carcinoma, composed of small nests of cancer cells surrounded by lacunar spaces. Invasive MPC is associated with poor prognosis. The nests of tumor cells in MPC reportedly exhibit reverse polarity, although the molecular mechanisms underlying MPC patterns are poorly understood. Using the cancer tissue-originated spheroid (CTOS) method, we previously reported polarity switching in colorectal cancer (CRC). When cultured in suspension, the apical membrane promptly switches from the outside surface of the CTOSs to the surface of the lumen inside the CTOSs under extracellular matrix (ECM)-embedded conditions, and vice versa. Here, we investigated two CTOS lines from CRC patient tumors with MPC lesions. Xenograft tumors from the CTOSs exhibited the MPC phenotype. The MPC-CTOSs did not switch polarity in vitro. Time-course analysis of polarity switching using real-time imaging of the apical membrane revealed that local switching was continually propagated in non-MPC-CTOSs, while MPC-CTOSs were unable to complete the process. Integrin β4 translocated to the outer membrane when embedded in ECM in both MPC and non-MPC-CTOSs. Protein levels, as well as the active form of RhoA, were higher in MPC-CTOSs. The suppression of RhoA activity by GAP overexpression enabled MPC-CTOSs to complete polarity switching both in vitro and in vivo, while overexpression of active RhoA did not affect polarity switching in non-MPC-CTOSs. Pretreatment with a ROCK inhibitor enabled MPC-CTOSs to complete polarity switching both in vitro and in vivo, although delayed treatment after becoming embedded in ECM failed to do so. Thus, the inability to switch polarity might be a cause of MPC, in which the aberrant activation of RhoA plays a critical role. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
To compare the hemostatic effects of commonly used concentrations of topical epinephrine in tympanoplasty.
Prospective, randomized, controlled clinical trial.
Patients undergoing tympanoplasty were randomized to receive topical epinephrine at 11,000 or 110,000. With the investigators blinded, hemostasis was assessed with a modified Boezaart scale. Vasoconstriction was measured by laser Doppler. Blood pressure and pulse were tracked.
Thirty patients, 4 to 84 years old, were studied, with 15 patients per group. Boezaart scores dropped a mean of 67% and 62% with 11,000 and 110,000, respectively (P= .44). Capillary blood flow decreased a mean of 50.4% and 50.9% with 11,000 and 110,000, respectively (P= .95). The mean change in heart rate and mean arterial pressure after topical epinephrine exposure were -4.9 and -0.73 beats per minute (P= .15), and -0.60 and -0.73 mmHg (P= .96) for 11,000 and 110,000 respectively. No adverse events occurred in either group.
Topical epinephrine at 110,000 has hemostatic efficacy comparable to 11,000 in tympanoplasty. Although both concentrations appear safe, use of topical epinephrine 110,000 should be considered over 11,000 to minimize the potential for adverse events.
2 Laryngoscope, 2021.
2 Laryngoscope, 2021.
Maxillary cancers are rare and aggressive tumors, which can spread beyond the sinus bony walls. Preoperative assessment of infiltration of maxillary sinus floor (MSF) is paramount for surgical planning, as palatomaxillary demolition significantly impacts patients’ quality of life. This study investigates the challenges involved in the preoperative and intraoperative evaluation of MSF infiltration and analyzes its prognostic relevance.
Retrospective case series.
A retrospective review of patients treated for sinonasal malignancies at a single Institution was performed. Patients receiving surgical-based treatment with curative intent for primary maxillary sinus cancers, between January 2000 and November 2019, were included.
A cohort of 118 patients was analyzed. By comparing intraoperative findings (endoscopic assessment and frozen sections) with preoperative radiological assessment, diagnostic changes with regard to MSF infiltration were found in 27.1% (32/118 cases). MSF infiltration negatively affected the prognosis in both univariate and multivariate analyses in the overall population. In the subgroup ofpT1-T3 tumors, MSF infiltration was significantly associated with reduced overall (P=.012), disease-free (P=.011), and distant recurrence-free (P=.002) survival rates. Conversely, pT classification was not able to stratify patients according to prognosis, mainly because early-staged cancers (pT1-T2) with MSF infiltration showed reduced survival rates, similar to those observed in pT3 cancers.
Preoperative imaging should be integrated with intraoperative findings based on endoscopic inspection and frozen sections. Future studies are required to investigate the opportunity to incorporate MSF infiltration in the TNM staging system, considering its crucial role in defining the extent of surgery and its potential as prognosticator.
4 Laryngoscope, 2021.
4 Laryngoscope, 2021.
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