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Background: Immune‐checkpoint inhibitors (ICIs) often cause immune‐related adverse events (irAEs). The spectrum of irAEs and their managements has been partially clarified, however the knowledge on time‐course of irAEs is not well understood. Methods: A retrospective study based on the medical record was performed. The study subjects were consisting of patients with various types of solid tumors for whom ICIs (nivolumab, pembrolizumab, durvalumab, atezolizumab, nivolumab plus ipilimumab) were used between April 2016 and October 2021. We focused on irAEs developed more than 1‐year after commencement ICIs (delayed irAE group) and compared with irAEs developed within 1‐year (non‐delayed irAE group) in terms of types and severity of irAEs. Results: A total of 336 patients were enrolled in the study. Eighty‐eight patients (26.2%) developed irAEs and 248 did not. Most of the patients developing irAEs were treated using PD‐L1/PD‐1 inhibitors. Eighty‐one patients (24.1%) in non‐delayed irAE group and 7 patients (2.1%) in delayed irAE group developed irAEs. The median onset of irAEs in the delayed irAE group was 18.6 months (range: 13.5–24.3). The types of irAEs observed in delayed irAE group were dermatitis (2 cases), pneumonitis (2 cases), nephritis (1 case), arthritis (1 case), and gastritis (1 case). The severity of irAEs was almost mild (≤G2), but one patient (.3%) developed G3 nephritis. Conclusion: PD‐L1/PD‐1 inhibitors frequently caused various irAEs but their severities were mostly tolerable. Few patients developed delayed irAE with mild toxities. [ABSTRACT FROM AUTHOR]

Objective: Respiratory epithelial adenomatoid hamartoma (REAH) is classified as a histopathologic diagnosis and often identified in sinus surgery for chronic rhinosinusitis (CRS). The purpose of this study was to clarify the frequency and predictors of REAH and prognosis of CRS with REAH in CRS cases. Methods: In the first study, we histologically reviewed sinonasal polyps and mucosal tissue specimens obtained from patients who underwent endoscopic sinus surgery (ESS) for CRS to reveal how many REAH were involved in ESS cases. We compared REAH and non‐REAH groups in terms of preoperative symptoms and endoscopic, imaging and blood examination findings to elucidate predictors of REAH genesis. In the second study, we compared the data 3 months after surgery such as endoscopic and imaging findings and olfactory test to evaluate prognosis of CRS with REAH. Results: The prevalence of REAH was 15.5% of all 304 cases in the first and second studies combined. Higher polyp score in the middle meatus was an independent predictor of the presence of REAH (p =.02). Presence of REAH was significantly associated with the enlargement of olfactory cleft polyps (p <.01), increasing postoperative scores of standard olfactory tests (p =.03), and decline of ratio of improvement (p <.01) measured using T&T olfactometry. Conclusions: Higher polyp score in the middle meatus is an independent predictor of REAH. Olfactory function is difficult to recover after surgery in REAH patients because it is associated with recurrent polyps in the olfactory cleft. [ABSTRACT FROM AUTHOR]

Objective: Head trauma can be a cause of refractory olfactory dysfunction due to olfactory nervous system injury. Anti‐inflammatory treatment using steroids or anti‐cytokine agents is known to contribute to functional recovery of the central and peripheral nervous systems in injury models, while there is a concern that they can induce adverse reactions. The present study examines if high‐dose immunoglobulin G (IgG) can facilitate olfactory functional recovery following injury. Methods: Olfactory nerve transection (NTx) was performed in OMP‐tau‐lacZ mice to establish injury models. High‐dose IgG was intraperitoneally injected immediately after the NTx and histological assessment of recovery within the olfactory bulb was performed at 5, 14, 42, and 100 days after the drug injection. X‐gal staining labeled degenerating and regenerating olfactory nerve fibers and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. Olfactory function was assessed using an olfactory avoidance behavioral test. Results: High‐dose IgG‐injected mice showed significantly smaller areas of injury‐associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. An olfactory avoidance behavioral test showed improved functional recovery in the IgG‐injected mice. Interpretation: These findings suggest that high‐dose IgG could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries. [ABSTRACT FROM AUTHOR]

Aim: We examined the effect of individualized occupational therapy (IOT) compared to the usual group occupational therapy (GOT) on the rehospitalization of patients with schizophrenia. Methods: A prospective cohort study included patients with schizophrenia who were discharged within 1 year from a psychiatric hospital. Time to rehospitalization by treatment group (GOT + IOT or GOT‐alone) was evaluated with Kaplan–Meier survival analysis. The impact of demographics and clinical factors associated with rehospitalization was investigated using Cox proportional hazards models. Results: Of the 111 patients who met the criteria, 54 were in the GOT + IOT group and 57 in the GOT‐alone group. Over the 2 years from discharge, the overall rehospitalization rate was 51.376% (56 patients); the GOT + IOT group demonstrated a significantly lower rehospitalization rate with 16 patients rehospitalized compared to 40 patients from the GOT‐alone group. Time to rehospitalization was significantly longer for the GOT + IOT group compared to those in the GOT‐alone group (P < 0.001). The multivariate Cox proportional hazards models showed that type of occupational therapy (hazard ratio [HR] = 0.543), medication adherence (HR = 0.343), access to resident support persons (HR = 0.450), and executive function at discharge (HR = 0.740) were all significantly associated with rehospitalization. Conclusion: Our results provide support for the prolonging effects of IOT in relation to rehospitalization and the reduction of rehospitalization risk compared to patients with schizophrenia who receive GOT alone, in addition to supporting good cognition at discharge and favorable medication adherence. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to assess the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan against locally advanced lower rectal cancer according to UDP‐glucuronosyltransferase 1A1 (UGT1A1) polymorphisms. Between 2009 and 2016, 46 patients with resectable rectal cancer (T3‐T4, N0‐N2, M0) received preoperative chemoradiotherapy consisting of 80 mg/m2 per day tegafur/gimeracil/oteracil (S‐1; days 1‐5, 8‐12, 22‐26, and 29‐33), 60 mg/m2 per day irinotecan (days 1, 8, 22, and 29), and 45 Gy radiation (1.8 Gy/day, 5 days per week for 5 weeks). Six to eight weeks after completing chemoradiotherapy, total mesorectal excision was carried out. Patients with UGT1A1 polymorphisms were divided into WT (n = 26), heterozygous (n = 15), and homozygous (n = 5) groups, the latter including double heterozygosities. We evaluated associations between clinical characteristics, including UGT1A1 polymorphisms, and chemoradiotherapy efficacy and toxicity. Incidence rates of grade 3+ neutropenia and diarrhea were 17.0% and 30.4%, respectively. Relative dose intensity was 89.3%. Pathological complete response rate (grade 3) was 26.1%, and the good response (grade 2/3) rate was 84.8%. UGT1A1 polymorphisms were significantly associated with neutropenia and pathological good responses, but not with diarrhea. UGT1A1 polymorphism was the only predictive factor for pathological good responses. Our results indicate that UGT1A1 polymorphism is a predictive factor to determine the clinical efficacy of preoperative chemoradiotherapy and hematological toxicity induced by chemoradiotherapy using irinotecan in locally advanced rectal cancer patients. We evaluated associations between clinical characteristics, including UGT1A1 polymorphisms, and chemoradiotherapy efficacy and toxicity. UGT1A1 polymorphisms were significantly associated with neutropenia and pathological good responses, but not with diarrhea. [ABSTRACT FROM AUTHOR]

Lynch syndrome ( LS) and familial adenomatous polyposis ( FAP) are major sources of hereditary colorectal cancer ( CRC) and are associated with other malignancies. There is some heterogeneity in management strategies in Japan. We undertook a survey of management of hereditary CRC in hospitals that are members of the Japan Society of Colorectal Cancer Research. One hundred and ninety departments responded, of which 127 were from designated cancer care hospitals ( DCCHs) according to the Japanese government. There were 25 488 operations for CRC in these departments in 2015. The DCCHs performed better with regard to usage of Japan Society of Colorectal Cancer Research guidelines, referring new CRC patients for LS screening, and having in-house genetic counselors and knowledge of treatment for LS. There were 174 patients diagnosed with LS and 602 undergoing follow-up in 2011-2015, which is fewer than the number expected from CRC operations in 2015. These numbers were not affected by whether the institution was a DCCH. Universal screening for LS was carried out in 8% of the departments. In contrast, 541 patients were diagnosed with FAP and 273 received preventive proctocolectomy/colectomy in 2011-2015. The DCCH departments undertook more surgery than non- DCCH departments, although most of the management, including surgical procedures and use of non-steroidal anti-inflammatory drugs, was similar. Management of desmoid tumor in the abdominal cavity differed according to the number of patients treated. In conclusion, there was heterogeneity in management of LS but not FAP. Most patients with LS may be overlooked and universal screening for LS is not common in Japan. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Previous reports have suggested that mucosal barrier failure allows lanthanum to stray into the lamina propria, and macrophages play an important role for the clearance. However, there is no report to analyze the polarity of phagocytizing macrophages. We suggested that M2 macrophage potentially played a major role in the clearance of lanthanum. Previous reports have suggested that mucosal barrier failure allows lanthanum to stray into the lamina propria, and macrophages play an important role for the clearance. However, there is no report to analyze the polarity of phagocytizing macrophages. We suggested that M2 macrophage potentially played a major role in the clearance of lanthanum. [ABSTRACT FROM AUTHOR]

The article focuses on a research related to development of an individualized occupational therapy programme and its effects on the neurocognition, symptoms and social functioning of patients with schizophrenia. It discusses use of Brief Assessment of Cognition in Schizophrenia—Japanese version (BACS-J), the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning scale. It concludes improvement in cognitive impairment and symptoms in patients with schizophrenia.

Summary The bacterial contamination of dried Japanese common squid was effectively controlled by regulating the distribution of two water species retained in a Japanese common squid mantle. The two water species were distinguished as water species-A1, a mobile-water species and water species-A2, a relatively restricted-water species. Water species-A1 and -A2 were effectively characterised by a physicochemical parameter, the correlation time ( τC, s), which was evaluated using a proton NMR analysis. The bacterial count was evaluated as a function of τC and the relative humidity (RH), and the results precisely demonstrated the existence of a critical τC (C τC = 10−8 s) at which the water species were divided into species-A1 (region I < C τC) and -A2 (region II > C τC). Bacterial growth was completely interrupted by species-A2 or by an RH lower than 30% (designated as RH30) at <103 CFU g−1. In region I, at higher than RH30, the dominant genera of the bacteria observed were identified as Micrococcus and Staphylococcus. [ABSTRACT FROM AUTHOR]

For the discrimination of water molecules during the squid-drying process, the water distribution was characterised by water proton NMR and moisture diffusivity ( De) analysis methods as a function of the water content ( W0). The proton NMR spectrum showed three peaks indicating three different species (species-A, -B, and -C) distributed in the squid muscle, each of which had a characteristic behaviour of the relaxation time ( T2) as a function of the W0. The 1/ T2 of species-A was drastically varied at W0 = 120%-d.b., indicating two further categories, i.e., species-A1 and -A2. Species-A1 is available at W0 > 120%-d.b. and was characterised as having De = 5.1 × 10−10 m2 s−1, activation energy of moisture diffusivity ( ED) = 17 kJ mol−1, and relaxation rate 1/ T2 = 74 s−1, as evaluated by the proton NMR spectrum without depending on W0. Species-A2 is available at W0 < 120%-d.b., indicating a distribution of De = 4.8 × 10−10–1.7 × 10−10 m2 s−1, ED = 25–35 kJ mol−1 and 1/ T2 = 1.8 × 103–1.5 × 102 s−1 with increasing W0. Species-A1 and -A2 were assigned as weakly restricted water and strongly restricted water, respectively. [ABSTRACT FROM AUTHOR]

Bioresorbable and functionally graded apatites (fg-HAp) ceramics, which are characterized by gradations in crystallinity and the grain size of hydroxyapatite (HAp:Ca10(PO4)6(OH)2), were designed using bovine bone by the calcination and partial dissolution–precipitation method. The fg-HAp ceramics had macropores of 100–600 μm originated from spongy bone, and micropores of 10–160 nm. Fg-HAp ceramics loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2/fg-HAp) were implanted into the subcutaneous tissue of rats. Eight weeks after the implantation, the surface and bulk degradations of the fg-HAp-containing body fluid occured, and small pieces of fg-HAp were incorporated into the induced bone and fatty marrow, suggesting that osteoinduction occurred in conjunction with bone remodeling. The rhBMP-2/fg-HAp ceramics developed could become a resorbable biomimetic material with fast bioresorption and osteoinduction characteristics. [ABSTRACT FROM AUTHOR]

SUMMARY 1. Arterial baroreflexes are suppressed in stressful conditions. Intense visual stimuli can cause a threatening sensation and produce defensive reactions. 2. The present study was designed to determine whether and how electrical stimulation of the optic tract (OT) affects arterial baroreflexes, especially the heart rate component, baroreflex vagal bradycardia (BVB), in rats. In chloralose– urethane anaesthetized, β-adrenoceptor-blocked rats, BVB was evoked by electrical stimulation of the aortic depressor nerve. 3. Electrical stimulation of the OT was found to not only increase blood pressure and heart rate, but also to inhibit BVB. To determine whether these responses were mediated by the lateral genticulate body and/or the superior colliculus, which are major target sites to which the OT projects, each was activated with electrical and chemical stimulation. 4. The lateral genticulate body did not respond to either electrical or chemical stimulation, whereas the superior colliculus increased blood pressure and heart rate while suppressing BVB following electrical stimulation. Essentially similar responses were observed following microinjection of the GABA antagonist bicuculline methiodide. 5. Optic tract-induced inhibition of BVB was abolished by bilateral destruction of the superior colliculus. Furthermore, this inhibition was also largely attenuated by destruction of the midbrain periaqueductal grey (PAG). 6. In conclusion, electrical stimulation of the OT increases blood pressure, heart rate and inhibits BVB. These responses are not mediated by the lateral genticulate body but are mediated by the superior colliculus. The PAG may participate in the subsequent mediation of the responses to electrical stimulation of the OT and the OT-induced inhibition of BVB may contribute to expression of a light-induced defence reaction. [ABSTRACT FROM AUTHOR]

Measures and compares the permeability and diffusivity of d-limonene vapor in nine polymeric sealant films at a vapor concentration of 0.719 mg/L over the range 25-45 degrees centigrade. Determination of the sorption of d-limonene by a temperature programmed desorption (TPD) method; Derivation of equations to predict permeability and diffusivity.

This paper describes a novel vertical power MOS-FET with low on-resistance and large avalanche current, called US-DMOS (U-grooved self-signed DMOS). It features a U-grooved self-aligned source and base con bets with respect to the gate electrode, which reduces the cell aim to two-thirds the conventional cell size and reduces the parasitic base resistance. Using three-dimensional simulation on this device structure, the reduction on the on-resistance by the formation of the U-groove and the increase of the avalanche current by the reduction of the base resistance were proved. In an n-channel test device with a drain current of 60 V, the on-resistance was 156 mωmm², which is 30 percent lower than in a comparable device with a conventional structure. In addition, the avalanche current was one order of magnitude higher in this device. [ABSTRACT FROM AUTHOR]

Objective: To examine the interaction between heme oxygenase 1 (HO-1), a stress-induced antiinflammatory protein, and tumor necrosis factor alpha (TNFalpha) in human peripheral blood monocytes., Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from healthy donors or from patients with rheumatoid arthritis (RA) receiving the anti-tumor necrosis factor alpha (anti-TNFalpha) monoclonal antibody infliximab. CD14+ cells were isolated by magnetic cell sorting, cultured with TNFalpha or auranofin, and transfected with a plasmid encoding HO-1 or an HO-1-specific small interfering RNA vector. Protein and messenger RNA (mRNA) levels were examined by immunoblotting and real-time polymerase chain reaction. Cytokine levels in culture supernatants were measured by enzyme-linked immunosorbent assay. HO-1 gene transcription was evaluated using a luciferase reporter gene assay. Actinomycin D and cycloheximide were used to monitor the stability of mRNA and protein., Results: HO-1 is constitutively expressed by CD14+ PBMCs from healthy donors. TNFalpha suppressed HO-1 expression by accelerating the decay of mRNA without affecting gene transcription or protein stability. Forced expression or selective knock-down of the HO-1 gene expression resulted in down-regulation or up-regulation, respectively, of proinflammatory cytokine synthesis by monocytes. Treatment with infliximab significantly increased HO-1 mRNA levels and reduced TNFalpha synthesis by PBMCs from RA patients., Conclusion: TNFalpha accelerated inflammatory responses by down-regulating HO-1 expression in human monocytes. TNF antagonists may block this TNF-dependent suppression of HO-1 expression, resulting in an amelioration of inflammation.