Antenatal and postpartum depression in women who conceived after infertility treatment: a longitudinal study.

BACKGROUND: Although the association between a history of infertility treatment and perinatal depression has been investigated, most research has been cross-sectional and has not used diagnostic assessment tools. AIMS: This study investigates longitudinally the association between a history of infertility treatment and perinatal depression using WHO-Composite International Diagnostic Interview 3.0 (WHO-CIDI 3.0) and the Edinburgh Postnatal Depression Scale (EPDS). METHODS: This study used data (N = 2,435) from the control group of a randomised controlled trial on a sample of pregnant women. Survival analysis was used to examine the influence of infertility treatment on perinatal depressive disorder evaluated by WHO-CIDI 3.0. The EPDS scores at four time points (T1 [baseline]: 18 ± 2 weeks gestation, T2: 32 weeks gestation, T3: 1 week postpartum, T4: 3 months postpartum) were analysed using generalised mixed model analysis. RESULTS: The risk of experiencing a major depressive episode evaluated by WHO-CIDI 3.0 did not significantly differ between women conceiving through infertility treatment and those conceiving spontaneously (adjusted hazard ratio = 1.64, p = 0.109). The longitudinal analysis demonstrated that EPDS scores significantly increased at T3 and T4 among women conceiving through infertility treatment compared with those conceiving spontaneously (adjusted estimates of fixed effect from T1 to T3: 1.17, p < 0.01; from T1 to T4: 0.71, p = 0.022). CONCLUSION: Women conceiving through infertility treatment were not found to have a higher risk of diagnosable perinatal depressive disorder than those conceiving naturally. However, a history of infertility treatment can marginally increase sub-clinical postpartum depressive symptoms.

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.

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.

[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.

[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.

[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.

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.

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.

Molecular mechanism underlying juvenile hormone-mediated repression of precocious larval-adult metamorphosis.

Juvenile hormone (JH) represses precocious metamorphosis of larval to pupal and adult transitions in holometabolous insects. The early JH-inducible gene Krüppel homolog 1 (Kr-h1) plays a key role in the repression of metamorphosis as a mediator of JH action. Previous studies demonstrated that Kr-h1 inhibits precocious larval-pupal transition in immature larva via direct transcriptional repression of the pupal specifier Broad-Complex (BR-C). JH was recently reported to repress the adult specifier gene Ecdysone-induced protein 93F (E93); however, its mechanism of action remains unclear. Here, we found that JH suppressed ecdysone-inducible E93 expression in the epidermis of the silkworm Bombyx mori and in a B. mori cell line. Reporter assays in the cell line revealed that the JH-dependent suppression was mediated by Kr-h1. Genome-wide ChIP-seq analysis identified a consensus Kr-h1 binding site (KBS, 14 bp) located in the E93 promoter region, and EMSA confirmed that Kr-h1 directly binds to the KBS. Moreover, we identified a C-terminal conserved domain in Kr-h1 essential for the transcriptional repression of E93 Based on these results, we propose a mechanism in which JH-inducible Kr-h1 directly binds to the KBS site upstream of the E93 locus to repress its transcription in a cell-autonomous manner, thereby preventing larva from bypassing the pupal stage and progressing to precocious adult development. These findings help to elucidate the molecular mechanisms regulating the metamorphic genetic network, including the functional significance of Kr-h1, BR-C, and E93 in holometabolous insect metamorphosis.

Comparison between wide-angle OCT angiography and ultra-wide field fluorescein angiography for detecting non-perfusion areas and retinal neovascularization in eyes with diabetic retinopathy.

PURPOSE: To compare the ability of wide-angle optical coherence tomography angiography (OCTA) with that of ultra-wide field fluorescein angiography (UWFFA) to detect non-perfusion areas (NPAs) or retinal neovascularization (NV) in eyes with diabetic retinopathy (DR). METHODS: Patients with DR underwent UWFFA using the Optos® panoramic 200Tx imaging system and wide-angle OCTA with 12 × 12 mm fields of five visual fixations using the PLEX Elite 9000®. We compared the abilities of UWFFA and OCTA to detect NPAs and NV. RESULTS: Fifty-eight eyes of 33 patients (mean age, 60.0 years old; female/male, 16/17) with DR were evaluated. NPAs were detected in 47 out of 58 eyes using UWFFA and in 48 eyes using OCTA. NVs were detected in 25 out of the 58 eyes using UWFFA and in 26 eyes using OCTA. The sensitivity for detection of NPA using OCTA was 0.98, and the specificity was 0.82. The sensitivity for detection of NV was 1.0, and the specificity was 0.97. CONCLUSION: The wide-angle OCTA seems to be clinically useful for the detection of NPAs or NV.

Krüppel Homolog 1 Inhibits Insect Metamorphosis via Direct Transcriptional Repression of Broad-Complex, a Pupal Specifier Gene.

The Broad-Complex gene (BR-C) encodes transcription factors that dictate larval-pupal metamorphosis in insects. The expression of BR-C is induced by molting hormone (20-hydroxyecdysone (20E)), and this induction is repressed by juvenile hormone (JH), which exists during the premature larval stage. Krüppel homolog 1 gene (Kr-h1) has been known as a JH-early inducible gene responsible for repression of metamorphosis; however, the functional relationship between Kr-h1 and repression of BR-C has remained unclear. To elucidate this relationship, we analyzed cis- and trans elements involved in the repression of BR-C using a Bombyx mori cell line. In the cells, as observed in larvae, JH induced the expression of Kr-h1 and concurrently suppressed 20E-induced expression of BR-C. Forced expression of Kr-h1 repressed the 20E-dependent activation of the BR-C promoter in the absence of JH, and Kr-h1 RNAi inhibited the JH-mediated repression, suggesting that Kr-h1 controlled the repression of BR-C. A survey of the upstream sequence of BR-C gene revealed a Kr-h1 binding site (KBS) in the BR-C promoter. When KBS was deleted from the promoter, the repression of BR-C was abolished. Electrophoresis mobility shift demonstrated that two Kr-h1 molecules bound to KBS in the BR-C promoter. Based on these results, we conclude that Kr-h1 protein molecules directly bind to the KBS sequence in the BR-C promoter and thereby repress 20E-dependent activation of the pupal specifier, BR-C. This study has revealed a considerable portion of the picture of JH signaling pathways from the reception of JH to the repression of metamorphosis.

A randomized, placebo- and sitagliptin-controlled trial of the safety and efficacy of omarigliptin, a once-weekly dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes.

AIMS: To assess the safety and efficacy of omarigliptin in Japanese patients with type 2 diabetes (T2D). METHODS: In a 24-week double-blind trial, 414 patients with T2D were randomized to omarigliptin 25 mg once weekly, sitagliptin 50 mg once daily or placebo. The double-blind period was followed by a 28-week open-label extension during which all patients received omarigliptin 25 mg once weekly. Efficacy endpoints were glycated haemoglobin (HbA1c), 2-hour postprandial glucose (PPG) and fasting plasma glucose (FPG) levels. RESULTS: After 24 weeks, the least squares (LS) mean change from baseline in HbA1c was -0.66% for omarigliptin, -0.65% for sitagliptin and 0.13% for placebo. The difference in LS mean for omarigliptin vs placebo was -0.80% ( P < .001). The difference in LS mean for omarigliptin vs sitagliptin was -0.02% (95% confidence interval -0.15, 0.12), which met the criterion for non-inferiority to sitagliptin. Both active treatments provided significant reductions in FPG and 2-hour PPG compared with placebo (P < .001). Over the 24-week double-blind period, there were no clinically meaningful differences in the incidence rates of adverse events among the treatment groups. There was 1 episode of symptomatic hypoglycaemia in the sitagliptin group and none in the omarigliptin or placebo groups. In the 28-week open-label period, omarigliptin provided persistent improvements in glycaemic control without notable change in safety profile compared with the double-blind period. Omarigliptin had no meaningful effect on body weight. CONCLUSIONS: In Japanese patients with T2D, omarigliptin 25 mg once weekly provided significant glucose-lowering compared with placebo and was non-inferior to sitagliptin 50 mg once daily. Omarigliptin was generally well tolerated for up to 52 weeks.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY REVEALS BLOOD FLOW IN CHOROIDAL NEOVASCULAR MEMBRANE IN REMISSION PHASE OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The aim of the study was to investigate blood flow in choroidal neovascular membrane in remission phase of neovascular age-related macular degeneration using optical coherence tomography (OCT) angiography. METHODS: OCT angiography was obtained in eyes with remission phase of neovascular age-related macular degeneration after treatments, defined as no exudative change (such as macular edema, subretinal fluid, and subretinal hemorrhage) observed in eyes without any treatment for neovascular age-related macular degeneration within the previous 6 months. Irregular blood flows shown in the segmentation of outer retina detected by OCT angiography were considered as blood flows in choroidal neovascular membrane. The vascular area and vessel density were obtained from OCT angiography images. RESULTS: Twenty eyes of 20 patients were included in this analysis. The blood flows in choroidal neovascular membrane were observed in all eyes (100%) using OCT angiography. The mean vascular area was 3.81 ± 3.41 mm and the mean vessel density of lesion was 28.9 ± 8.2%. The vessel density was significantly correlated with best-corrected visual acuity and duration of remission (best-corrected visual acuity: P = 0.008, r = -0.576; duration of remission: P = 0.017, r = -0.525, respectively). CONCLUSION: Optical coherence tomography angiography revealed that blood flows in choroidal neovascular membrane remained in eyes with clinically inactive neovascular age-related macular degeneration.

The Promoting Effect of the Extracellular Matrix Peptide TNIIIA2 Derived from Tenascin-C in Colon Cancer Cell Infiltration.

The extracellular matrix (ECM) molecule tenascin C (TNC) is known to be highly expressed under various pathological conditions such as inflammation and cancer. It has been reported that the expression of TNC is correlated with the malignant potential of cancer. In our laboratory, it was found that the peptide derived from the alternative splicing domain A2 in TNC, termed TNIIIA2, has been shown to influence a variety of cellular processes, such as survival, proliferation, migration, and differentiation. In this study, we investigated the effect of TNC/TNIIIA2 on the invasion and metastasis of colon cancer cells, Colon26-M3.1, or PMF-Ko14, using an in vitro and in vivo experimental system. The degree of cell invasion was increased by the addition of TNC and TNIIIA2 in a dose-dependent manner. The invasion by TNC and TNIIIA2 were suppressed by an MMP inhibitor or TNIIIA2-blocking antibody. In an in vivo experiment, pulmonary metastasis was promoted conspicuously by the addition of TNIIIA2. In this study, we found that colon cancer cell invasion and metastasis was accelerated by TNC/TNIIIA2 via MMP induction. This result suggests the possibility of a new strategy targeting TNC/TNIIIA2 for colon cancer.

Reactive swelling of the regional lymph nodes in patients with stage II colorectal cancer as a prognostic factor.

The aim of this study was to examine the relationship between reactive swelling of regional lymph node (LN) and survival in colorectal carcinoma. We retrospectively studied 170 patients with surgically resected colorectal carcinoma histopathologically diagnosed as stage II (pStage II). These patients were classified into two groups:a) a "reactive LN swelling" group (clinically diagnosed as positive for LN metastasis, but pathologically negative) and b) a "no LN swelling" group. Survival analyses of the two groups showed that overall survival (OS) and disease-specific survival (DSS) were longer in the reactive LN swelling group than in the no LN swelling group in patients with total colorectal and right-sided colon cancer. Multivariate analyses revealed that reactive LN swelling was an independent prognostic factor in OS and DSS in patients with right-sided colon cancer. Reactive swelling of regional LN is regarded as an expression of local immune responses, which could explain the present results.

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.

Leucine-rich alpha-2 glycoprotein is useful in predicting clinical relapse in patients with Crohn's disease during biological remission.

Background/Aims: Serum leucine-rich alpha-2 glycoprotein (LRG) is a potential biomarker of Crohn's disease (CD). This study aimed to evaluate the usefulness of LRG in predicting clinical relapse in patients in remission with CD. Methods: This retrospective observational study assessed the relationships among patient-reported outcome (PRO2), LRG, and other blood markers. The influence of LRG on clinical relapse was assessed in patients in remission with CD. Results: Data of 94 patients tested for LRG between January 2021 and May 2023 were collected. LRG level did not correlate with PRO2 score (ρ = 0.06); however, it strongly correlated with C-reactive protein (CRP) level (r=0.79) and serum albumin level (r=-0.70). Among 69 patients in clinical remission, relapse occurred in 22 patients (31.9%). In the context of predicting relapse, LRG showed the highest area under the curve, followed by CRP level, platelet count, and albumin level. Multivariate analysis revealed that only LRG (P= 0.02) was an independent factor for predicting clinical remission. The cumulative non-relapse rate was significantly higher in patients with LRG < 13.8 µg/mL than in patients in remission with LRG ≥ 13.8 µg/mL and normal CRP level (P= 0.002) or normal albumin level (P= 0.001). Cumulative non-relapse rate was also higher in patients with LRG < 13.8 µg/mL compared to those with LRG ≥ 13.8 µg/mL in patients with L3 or B2+B3 of Montreal calcification. Conclusions: LRG is useful in predicting clinical relapse in patients with CD during biological remission. LRG is a useful biomarker for predicting prognosis, even in patients with intestinal stenosis, or previous/present fistulas.