Endoscopic assessment of the J pouch in ulcerative colitis: A narrative review.

Patients with ulcerative colitis sometimes need a total colectomy with ileal pouch-anal anastomosis due to medically refractory disease or colitis-associated neoplasia. Up to 50% of patients with ulcerative colitis postoperatively develop pouchitis and the rate of chronic inflammatory pouch conditions requiring pouch excision or diverting ileostomy is reported to be 10%. In order to diagnose and monitor pouchitis, pouchoscopy is essential to assess endoscopic inflammatory findings of the J pouch and to survey neoplasia development, particularly in the remnant distal rectum. However, endoscopic protocols for the evaluation of the pouch may not be standardized worldwide and the reliability of existing disease activity indices for pouchitis has been questioned due to the lack of validation. Recently, reliable endoscopic scoring systems based on an observation of the anatomical location of the J pouch were reported and a significant association between the distribution pattern of endoscopic inflammation (i.e., endoscopic phenotype) and pouch outcomes was also uncovered. In this review, we discuss how to survey the J pouch using pouchoscopy, endoscopic indices for pouchitis disease activity, endoscopic phenotypes and classification, and the pathological mechanisms of pouchitis phenotype in patients with ulcerative colitis.

Functional variants in a TTTG microsatellite on 15q26.1 cause familial nonautoimmune thyroid abnormalities.

Insufficient thyroid hormone production in newborns is referred to as congenital hypothyroidism. Multinodular goiter (MNG), characterized by an enlarged thyroid gland with multiple nodules, is usually seen in adults and is recognized as a separate disorder from congenital hypothyroidism. Here we performed a linkage analysis of a family with both nongoitrous congenital hypothyroidism and MNG and identified a signal at 15q26.1. Follow-up analyses with whole-genome sequencing and genetic screening in congenital hypothyroidism and MNG cohorts showed that changes in a noncoding TTTG microsatellite on 15q26.1 were frequently observed in congenital hypothyroidism (137 in 989) and MNG (3 in 33) compared with controls (3 in 38,722). Characterization of the noncoding variants with epigenomic data and in vitro experiments suggested that the microsatellite is located in a thyroid-specific transcriptional repressor, and its activity is disrupted by the variants. Collectively, we presented genetic evidence linking nongoitrous congenital hypothyroidism and MNG, providing unique insights into thyroid abnormalities.

Efficacy of upadacitinib in the achievement of clinical and endoscopic remission in hospitalized patients with ulcerative colitis.

Janus kinase (JAK) inhibitors have been developed and are clinically available for management of active UC patients although most studies have been conducted for the outpatients and few studies have demonstrated its efficacy in endoscopic and histological remission of hospitalized patients with UC. The aim of the present study was to investigate the efficacy of upadacitinib, which is a novel selective JAK1 inhibitor, in the treatment of ulcerative colitis. We present the cases of three hospitalized patients with ulcerative colitis who achieved clinical remission after significant and rapid improvement with upadacitinib. While upadacitinib was used as the second-line treatment for patients with insufficient treatment effects for corticosteroids or ustekinumab, a patient received it just after admission because they were steroid dependent and previously used advanced therapy before hospitalization. All patients demonstrated rapid clinical responses within 7 days and the partial Mayo scores were 0 at week 8. All patients achieved confirmed endoscopic and histological remissions. We conclude that upadacitinib is a potential treatment option for hospitalized patients with an inadequate response to other biologics and JAK inhibitors.

Combined serum albumin, fecal immunochemical test, and leucine-rich alpha-2 glycoprotein levels for predicting prognosis in remitting patients with ulcerative colitis.

This study investigated the usefulness of serum leucine-rich alpha-2 glycoprotein (LRG) and fecal immunochemical tests (FIT) for predicting relapse in patients with ulcerative colitis (UC). Data of 194 patients tested for LRG between January 2020 and June 2022 were retrospectively collected and clinical characteristics were recorded. LRG was strongly correlated with CRP levels and it had a moderately negative correlation with albumin levels, whereas FIT was not significantly correlated with either CRP or albumin levels. Furthermore, the median serum albumin and FIT were significantly different between patients with or without clinical relapse; while the LRG level was not associated with clinical relapse. Although LRG is not an independent factor for predicting clinical relapse, the cumulative remission rate was significantly higher in patients with higher albumin than in those with lower albumin. Furthermore, the combination of FIT and albumin was useful for predicting for relapse, patients with higher FIT and lower albumin tended to have higher relapse rates than those with both lower FIT and albumin and those with lower FIT and higher albumin. Our study indicated that serum albumin level is useful for predicting relapse, even in remitting outpatients. Although LRG is not an independent factor for predicting clinical relapse, it is useful for identifying patients that are likely to relapse when combined serum albumin or FIT results.

Left or right, that is the question: use of egocentric frame of reference and the right-eye advantage for understanding gestural signs in bottlenose dolphins (Tursiops truncatus).

How do bottlenose dolphins visually perceive the space around them? In particular, what cues do they use as a frame of reference for left-right perception? To address this question, we examined the dolphin's responses to various manipulations of the spatial relationship between the dolphin and the trainer by using gestural signs for actions given by the trainer, which have different meanings in the left and right hands. When the dolphins were tested with their backs to the trainer (Experiment 1) or in an inverted position underwater (Experiments 2 and 3), correct responses from the trainer's perspective were maintained for signs related to movement direction instructions. In contrast, reversed responses were frequently observed for signs that required different sounds for the left and right hands. When the movement direction instructions were presented with symmetrical graphic signs such as " × " and "●", accuracy decreased in the inverted posture (Experiment 3). Furthermore, when the signs for sounds were presented from either the left or right side of the dolphin's body, performance was better when the side of the sign movement coincided with the body side on which it was presented than when it was mismatched (Experiment 4). In the final experiment, when one eye was covered with an eyecup, the results showed that, as in the case of body-side presentation, performance was better when the open eye coincided with the side on which the sign movement was presented. These results indicate that dolphins used the egocentric frame for visuospatial cognition. In addition, they showed better performances when the gestural signs were presented to the right eye, suggesting the possibility of a left-hemispheric advantage in the dolphin's visuospatial cognition.

Orientational Control of Circularly Polarized Luminescence from Pyrene Clusters by Using a DNA Scaffold.

Invited for the cover of this issue is the group of Hiromu Kashida and Hiroyuki Asanuma at Nagoya University and co-workers. The image depicts the orientation dependence of circularly polarized luminescent. Read the full text of the article at 10.1002/chem.202300182.

Orientational Control of Circularly Polarized Luminescence from Pyrene Clusters by Using a DNA Scaffold.

We have investigated the chiroptical activities of pyrene clusters incorporated within a DNA duplex. Three pyrene derivatives were prepared on d-threoninol linkers to allow incorporation within a DNA strand. DNA scaffolds containing dimers, tetramers, and hexamers of the pyrene derivatives were prepared. The homodimers of 1- and of 4-pyrenecarboxylic acid, but not 2-pyrenecarboxylic acid, emitted intense circularly polarized luminescence signals. Although increasing the number of pyrene units weakened the signal, insertion of natural base pairs between two dimers enhanced its intensity. Interestingly, circularly polarized luminescence intensities varied non-monotonically depending on the number of intervening base pairs, thus indicating the importance of orientation between pyrene dimers. The results presented here could lead to the development of bright circularly polarized luminescence materials and probes.

[Experience with a New Negative Pressure Incisional Wound Management System in Cardiac Surgery].

We report on the efficacy of the Prevena incisional wound management system, a negative pressure wound care system, in patients at a high risk of wound infection following cardiac surgery. METHODS: Ten patients with a mean Fowler risk score of 4.6( 1.6~9.9) were included. The Prevena system was applied immediately after surgery and used for 5 days while negative pressure of -125 mmHg was continuously applied, and the condition of the wound and surrounding skin was evaluated immediately after removal of the Prevena system. RESULT: Ten patients had completely healed wounds, and no skin damage around the wound due to negative pressure after removal of the Prevena system was observed. No skin damage was observed around the wound after removal of the Prevena system, and no wound complications occurred until discharge. CONCLUSIONS: The Prevena system is safe, easy to use, and useful for wound healing in patients at a high risk for wound complications after cardiac surgery.

[Lymphocytic colitis caused by medicine ingredient modification].

A 49-year-old woman was referred to our hospital for further evaluation and treatment of diarrhea. Colonoscopic findings revealed indistinct vascular patterns and extensive edema in a colon segment, and white granular mucosa and crack-like appearance in the sigmoid colon and rectum. She was diagnosed with lymphocytic colitis (LC) based on lymphocytic infiltration into the epithelium on histopathological examination. Diarrhea symptoms resolved after long-term medication withdrawal. This medicine's composition was changed 4 years ago and this modification possibly triggered LC.

TP53 positivity combined with high fibrinogen expression defines a subtype of oral squamous cell carcinoma with an unfavorable prognosis.

The number of deaths due to oral squamous cell carcinoma (OSCC), a malignant tumor of the oral cavity, is on the increase. We examined fibrinogen (FIB) expression in patients with OSCC and developed novel immunoprofile classification methods that include FIB. The plasma FIB level in patients with OSCC was elevated compared with that in patients with non-tumor oral disease (non-T); using a cut-off point of 342 mg/dL, we found the area under the curve-receiver operating characteristic level for OSCC was 0.745. Similarly, FIB expression in OSCC tissues was significantly higher compared with that in non-T tissues. Hierarchical clustering based on the immunoprofile of several markers including FIB, p53, and p16 revealed four groups that could be used to categorize OSCC cases (referred to as immunoprofile subtypes [IPS], I-IV). Tumors in IPS-II, which were FIB+/p53+, were associated with a significantly worse overall survival (OS) when compared with the other subtypes. We conclude that our IPS classification system can facilitate prognostic evaluation in OSCC, and that quantification of FIB is an important component of the classification strategy for this disease.

[A case of juvenile gastric polyposis with gastric cancer successfully treated by laparoscopic total gastrectomy -review of 36 reported cases in Japan].

A 43-year-old woman was suffering from epigastric pain. Her gastroscopy revealed polyposis of the stomach, and her biopsy revealed a hyperplastic polyp. During the 18-month follow-up, the polyps proliferated, and the patient was referred to our institute for further investigation and treatment. A juvenile gastric polyposis diagnosis was made. She refused to have the surgery despite the fact that it was necessary due to the anemia and hypoalbuminemia she was experiencing. Endoscopic biopsy results revealed gastric cancer at a follow-up visit 2 years and 3 months later; thus, a laparoscopic total gastrectomy was performed. Pathological examination revealed adenocarcinomas that were scattered and well-differentiated, with hyperplastic polyps in the background. No lymph node metastasis was found. Despite the fact that juvenile gastric polyposis is a pathologically benign disease, there have been numerous case reports of surgery being performed due to anemia, hypoalbuminemia, or gastric cancer associated with the disease. When gastric cancers are discovered in cases of juvenile gastric polyposis, they are usually in an early stage, making them a good candidate for laparoscopic total gastrectomy.

A Pyrene-Modified Serinol Nucleic Acid Nanostructure Converts the Chirality of Threoninol Nucleic Acids into Circularly Polarized Luminescence Signals.

Herein is reported a circularly polarized luminescent (CPL) probe that can respond to the chirality of nucleic acids. An achiral nanostructure was prepared by the hybridization of symmetric serinol nucleic acid (SNA) containing pyrene-modified residues. When chiral oligomers that were complementary to the SNA were added, they induced helicity into the SNA nanowire. Efficient circular dichroism (CD) signal amplification was observed when pyrene was attached to uracil bases through a rigid alkynyl linker. Both CPL and CD signals were observed; they depended on the chirality of the added acyclic threoninol nucleic acid (aTNA) oligomer. This system can be used to convert the chirality of chiral biomolecules into chiroptical signals.

Perylene-Cy3 FRET System to Analyze Photoactive DNA Structures.

We report a new Förster resonance energy transfer (FRET) system for structural analyses of DNA duplexes using perylene and Cy3 as donor and acceptor, respectively, linked at the termini of a DNA duplex via D-threoninol. Experimentally obtained FRET efficiencies were in good agreement with theoretical values calculated based on canonical B-form DNA. Due to the relatively long Förster radius, this system can be used to analyze large DNA structures, and duplexes containing photo-reactive molecules can be analyzed since perylene can be excited with visible light. The system was used to analyze a DNA duplex containing stilbene, demonstrating that in the region of the stilbene cluster the duplex adopts a ladder-like structure rather than helical one. Upon photodimerization between stilbene residues, FRET efficiencies indicated the reaction does not disturb DNA duplex. This FRET system will be useful for analysis of photoreactions of nucleobases as well as a wide range of nucleic acid structures.

Volatile Anesthetic Sevoflurane Precursor 1,1,1,3,3,3-Hexafluoro-2-Propanol (HFIP) Exerts an Anti-Prion Activity in Prion-Infected Culture Cells.

Prion disease is a neurodegenerative disorder with progressive neurologic symptoms and accelerated cognitive decline. The causative protein of prion disease is the prion protein (PrP), and structural transition of PrP from the normal helix rich form (PrPC) to the abnormal ß-sheet rich form (PrPSc) occurs in prion disease. While so far numerous therapeutic agents for prion diseases have been developed, none of them are still useful. A fluorinated alcohol, hexafluoro isopropanol (HFIP), is a precursor to the inhalational anesthetic sevoflurane and its metabolites. HFIP is also known as a robust α-helix inducer and is widely used as a solvent for highly aggregated peptides. Here we show that the α-helix-inducing activity of HFIP caused the conformational transformation of the fibrous structure of PrP into amorphous aggregates in vitro. HFIP added to the ScN2a cell medium, which continuously expresses PrPSc, reduced PrPSc protease resistance after 24-h incubation. It was also clarified that ScN2a cells are more susceptible to HFIP than any of the cells being compared. Based on these findings, HFIP is expected to develop as a therapeutic agent for prion disease.

Investigation of visual and physical factors associated with inadequate instillation of eyedrops among patients with glaucoma.

PURPOSE: The aim of this study was to investigate the frequency of eyedrop instillation failure and its related physical and visual function factors among glaucoma patients who used hypotensive eyedrops daily. SUBJECTS AND METHODS: Patients with a history of self-instillation of one or more ocular hypotensive ophthalmic solutions for six or more months were enrolled. Definitions of instillation failure were eyedrop instillation other than on the eye surface; eyedrop contact with eyelashes; eyedrop bottle tip contact with the eyelashes, eye surface or ocular adnexa; or two or more drops instilled with one instillation trial. To clarify factors related to instillation failure, we used visual function tests and investigated cervical spine extension angles during instillation, pinching strength, physical ataxia (evaluated using the Scale for the Assessment and Rating of Ataxia), motor dysfunction of the upper limbs (evaluated using the Disabilities of the Arm, Shoulder and Hand questionnaire), and vision quality (evaluated using the National Eye Institute Visual Function Questionnaire 25). RESULTS: Of 103 total subjects, 61.2% satisfied the definition of instillation failure. Instillation of the eyedrop other than at the cul-desac (76.2%) was the most frequent reason for failure, followed by contact of the tip of the eyedrop bottle (22.2%) and instillation of the same or more than two eyedrops in a single attempt (11.1%). Advanced age, a shallow cervical spine extension angle, weak pinching strength, poor motor dysfunction of the upper limbs, the degree of ataxia, poor best-corrected visual acuity, and visual field scores were significant risk factors for instillation failure. Vision quality may have some relation to instillation failure. CONCLUSION: It is highly recommended that instillation failure be routinely investigated even among patients with adequate experience using eyedrops and that correct therapies are chosen in a patient-based fashion.

Antiemetic Efficacy of Adding Olanzapine 5 mg to Aprepitant, Palonosetron and Dexamethasone-Sparing After Day Two for Cancer Patients Receiving Anthracycline and Cyclophosphamide.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) decrease patient quality of life (QOL). We evaluated the efficacy of adding 5 mg Olz to a three-drug steroid-sparing antiemetic regimen (aprepitant, palonosetron, and dexamethasone-sparing after day two) for breast cancer (BC) patients receiving anthracycline plus cyclophosphamide (AC) chemotherapy. PATIENTS AND METHODS: We retrospectively reviewed the records of 177 BC patients with no previous highly emetogenic chemotherapy history receiving AC plus the steroid-sparing three-drug regimen or the steroid-sparing four-drug regimen including Olz 5mg at our hospital between January 2012 and December 2018. The primary endpoint was complete response (CR), defined as no vomiting and no usage of rescue medication during the first AC cycle. We analyzed the odds ratio (OR) of the CR with 95% confidence interval (CI) in the three-drug group against the four-drug group. The OR was adjusted for types of anticancer drugs by the Cochran-Mantel-Haenszel (CMH) test. Secondary endpoints were incidences of nausea, anorexia, fatigue, and somnolence during the first cycle. RESULTS: Compared to the three-drug group, the four-drug group demonstrated high incidence of no vomiting (71% vs 95%), a similar incidence of no rescue medication usage (50% vs 51%), and a similar CR rate (45% vs 49%). The OR of the CR rate in the three-drug group against the four-drug group after CMH adjustment for drug type was 0.958 (95% CI, 0.46-1.98). Compared to the three-drug group, the four-drug group demonstrated identical incidence of nausea (66%), but lower incidences of anorexia (78% vs 35%) and fatigue (86% vs 73%). The incidence of somnolence in the four-drug group was 49%. We did not have data of somnolence for the three-drug group in the records. CONCLUSION: Adding 5 mg Olz to the steroid-sparing three-drug combination can reduce vomiting, anorexia, and fatigue, although there was no difference in CR rate.

Quantifying the inundation impacts of earthquake-induced surface elevation change by hydrological and hydraulic modeling.

Current estimates of flood hazards are often based on the assumption that topography is static. When tectonic and/or anthropogenic processes change the land surface elevation, the spatial patterns of floods might also change. Here, we employ the hydrological and hydraulic modeling to simulate floods in the Kujukuri Plain, Japan, in the years 2004 and 2013, when two severe floods occurred. In between the two floods, land surface elevations were changed by the 2011 Tohoku-Oki earthquake. The effects of land surface elevation changes on inundation areas were quantified by changing input topographies. Our results showed that, without taking into account land surface elevation changes, around 10% of inundation areas were underestimated at the time of flood events in the year 2013. The spatial distribution of inundation locations varied with local topographical features, for example, the areas with backmarsh and valley fill deposits were sensitive to the extent of inundation by land surface elevation changes. The sub-watershed near the coastal shoreline having below-zero meter elevation areas showed that the earthquake-induced land surface elevation changes exacerbated an additional 22% inundation area. This study suggests that the inundation areas will increase in catchments suffering severe settlements, which highlights the necessity of taking into account the spatio-temporal changes of land surface elevations on the assessment of flood hazards.

THE CORRELATION BETWEEN AQUEOUS VASCULAR ENDOTHELIAL GROWTH FACTOR LEVEL AND CLINICAL ACTIVITY IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The aim of the current study was to investigate the correlation between the pretreatment aqueous level of vascular endothelial growth factor (VEGF) and clinical activity in neovascular age-related macular degeneration. METHODS: Patients with neovascular age-related macular degeneration treated by intravitreal ranibizumab injections and followed for 12 months were included in the current study. The treatment regimen consisted of three consecutive monthly intravitreal ranibizumab injections (loading treatment) followed by a pro re nata (PRN) treatment regimen. The aqueous VEGF levels were measured by enzyme-linked immunosorbent assay using aqueous humor samples obtained just before the first intravitreal ranibizumab injections. RESULTS: Sixty-four eyes of 64 patients were included in the current study. The mean number of intravitreal ranibizumab injections during 12 months was 4.6 ± 1.4, and 17 eyes had no recurrence after loading treatment. The mean aqueous VEGF level was significantly higher in eyes with recurrence after loading treatment than in eyes without recurrence (107.6 vs. 83.8 pg/mL, respectively; P = 0.04) and significantly higher in eyes with recurrence within 3 months after loading treatment than in other eyes (114.9 vs. 86.7 pg/mL, respectively; P < 0.01). CONCLUSION: Pretreatment aqueous VEGF level was significantly correlated with the likelihood of recurrence in neovascular age-related macular degeneration. The measurement of pretreatment aqueous VEGF level may be useful to determine the best treatment options for patients with neovascular age-related macular degeneration.

Comparison of Efficacy of Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Co-Transporter 2 Inhibitors Between Japanese and Non-Japanese Patients: A Meta-Analysis.

We explored efficacy of dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose co-transporter 2 inhibitors (SGLT2is) between Japanese and non-Japanese patients with type 2 diabetes mellitus by conducting a systematic review and meta-analysis. A literature search of public databases before May 2017 identified 91 (DPP-4i) and 63 (SGLT2i) randomized placebo-controlled trials (> 12-week treatment). Multivariate meta-regression analysis identified baseline hemoglobin A1c (HbA1c) levels and placebo responses as covariates affecting efficacy of two agent classes independently of study region (Japanese/non-Japanese). When accounted for covariates, DPP-4i caused more pronounced HbA1c reduction in Japanese studies than in non-Japanese studies by 0.18% difference (P < 0.05) while causing no difference in fasting plasma glucose reduction between regions. On the other hand, when adjusted by baseline HbA1c levels and placebo responses, efficacy of SGLT2i were comparable between regions. The contrasting results for two agent classes indicate that drug efficacy is affected by different pathophysiology at its therapeutic action point.

Third generation impedimetric sensor employing direct electron transfer type glucose dehydrogenase.

Faradaic electrochemical impedance spectroscopy (faradaic EIS) is an attractive measurement principle for biosensors. However, there have been no reports on sensors employing direct electron transfer (DET)-type redox enzymes based on faradaic EIS principle. In this study, we have attempted to construct the 3rd-generation faradaic enzyme EIS sensor, which used DET-type flavin adenine dinucleotide (FAD) dependent glucose dehydrogenase (GDH) complex, to elucidate its characteristic properties as well as to investigate its potential application as the future immunosensor platform. The gold disk electrodes (GDEs) with DET-type FADGDH prepared using self-assembled monolayer (SAM) showed the glucose concentration dependent impedance change, which was confirmed by the change in the charge transfer resistance (Rct). The Δ(1/Rct) values were also affected by DC bias potential and the length of SAM. Based on the Nyquist plot and Bode plot simulations, glucose sensing by imaginary impedance monitoring under fixed frequency (5 mHz) was carried out, revealing the higher sensitivity at low glucose concentration with wider linear range (0.02-0.2 mM). Considering this high sensitivity toward glucose, the 3rd-generation faradaic enzyme EIS sensor would provide alternative platform for future impedimetric immunosensing system, which does not use redox probe.