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Objectives: The prognosis of patients with colorectal diverticular perforations requiring surgery is poor, and the efficacy of polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) in these patients has not yet been established. In the present study, we evaluated the prognostic factors and the efficacy of PMX-DHP in surgically treated patients with perforated colorectal diverticula. Methods: Of the 116 patients with colorectal perforations who underwent emergency surgery at our hospital between April 2018 and May 2023, we retrospectively reviewed 46 patients with perforated colorectal diverticula. Preoperative, surgical, and postoperative factors were compared between the survival and mortality groups. Subgroup analysis was performed to evaluate the efficacy of PMX-DHP in severe cases. Results: The postoperative mortality group included 7 patients (15.2%), and PMX-DHP was performed in 14 (30.4%). PMX-DHP was performed significantly more often in the mortality group (P

1,2,4-Triazole and 1,2,4-triazoline are important components of bioactive molecules and catalysts employed in organic synthesis. Therefore, the efficient synthesis of these components has received significant research attention. However, studies on their structural diversity remain lacking. Previously, we developed chiral phase-transfer-catalyzed asymmetric reactions of α-imino carbonyl compounds with α,β-unsaturated carbonyl compounds and haloalkanes. In this study, we demonstrate the formal [3 + 2] cycloaddition reaction of α-imino esters with azo compounds under Brønsted base catalysis, resulting in the corresponding 1,2,4-triazolines in high yields. The results revealed that a wide range of substrates and reactants can be applied, irrespective of their steric and electronic characteristics. The present reaction made the general preparation of 3-aryl pentasubstituted 1,2,4-triazolines possible for the first time. Furthermore, a mechanistic study suggested that the reaction proceeds without isomerization into the aldimine form.

There has been a great focus on halogen-bonding as a unique interaction between electron-deficient halogen atoms with Lewis basic moieties. Although the application of halogen-bonded atoms in organic chemistry has been eagerly researched in these decades, the development of chiral molecules with halogen-bonding functionalities and their utilization in asymmetric catalysis are still in the\ir infancy. We have previously developed chiral halonium salts with amide functionalities, which behaved as excellent catalysts albeit in only two reactions due to the lack of substrate activation abilities. In this manuscript, we have developed chiral halonium salts with an N-nitrosamine moiety and applied them to the Mannich reaction of isatin-derived ketimines with malonic esters. The study focused on our novel bromonium salt catalyst which provided the corresponding products in high yields with up to 80% ee. DFT calculations of the chiral catalyst structure suggested that the high asymmetric induction abilities of this catalyst are due to the Lewis basic role of the N-nitrosamine part. To the best of our knowledge, this is the first catalytic application of N-nitrosamines.

Yokukansankachimpihange is a Japanese herbal medicine reported to benefit anxiety and sleep disorders, and it has recently been introduced to treat behavioral and psychological symptoms of dementia. There are no multicenter studies of its effectiveness regarding dementia in Japan, and this study's main objective was to clarify the effects of Yokukansankachimpihange on behavioral and psychological symptoms of dementia in a sample of patients from multiple healthcare centers. Nine facilities affiliated with Osaka Association of Psychiatric Clinics participated in November 2013 through April 2015 and provided 32 Alzheimer's disease patients to whom Yokukansankachimpihange was orally administered for 8 weeks. During the study, the patients continued their regular medication regimens. Behavioral and psychological symptoms of dementia (Behavioral Pathology in Alzheimer's Disease Rating Scale [Behave-AD]), core symptoms [Mini-Mental State Examination (MMSE)], activities of daily living [Nishimura Activity of Daily Living Scale (N-ADL)], and gastrointestinal symptoms (nausea/vomiting, loss of appetite, gastric discomfort, constipation, and diarrhea) were measured at baseline, after 4 weeks of treatment and after 8 weeks of treatment. Yokukansankachimpihange was orally administered at a dosage of 7.5 g twice daily before or between meals for 8 weeks. The Behave-AD mean score significantly improved after 8 weeks of treatment. There were no significant changes in MMSE, N-ADL, or gastrointestinal symptoms; however, decreased gastrointestinal scores were observed after 8 weeks. There were no side effects related to Yokukansankachinpihange. Pharmaceutical treatments are important for treating behavioral and psychological symptoms of dementia, and this study confirmed Yokukansankachimpihange's efficacy for treating Alzheimer's disease. Because the aggressiveness and sleep disorder components of the Behave-AD construct were the symptoms most improved and those symptoms are known to significantly burden dementia patients' caregivers, Yokukansankachimpihange's efficacy might indirectly relieve these caregivers' burden of care.

The management of grade 1 checkpoint inhibitor pneumonitis (CIP) is to withhold immune checkpoint inhibitors; however, the natural history of this condition is unknown. We herein report the case of a woman with squamous cell lung cancer who was a long-term survivor after CIP. After 4 rounds of treatment with nivolumab, a chest CT revealed a reticular pattern and ground-glass attenuation with shrinkage of the primary nodule. Nivolumab treatment was withheld without the administration of steroids. Although she remained asymptomatic, subsequent images revealed an increasing interstitial shadow until 2 months after the stop of nivolumab treatment. Thereafter, the interstitial shadow began to improve spontaneously without steroid treatment. Moreover, although the patient has not received additional therapy, disease control of lung cancer has been obtained within a follow-up period of more than 3 years. Although the exacerbation of CIP may appear on images for several months, asymptomatic cases can be followed without the administration of steroids. If the tumor had already responded prior to the onset of CIP, a favorable long-term prognosis can be expected.

Cataplexy, an emotion-triggered sudden loss of muscle tone specific to narcolepsy, is tightly associated with hypocretin deficiency. Using hypocretin receptor 2 gene (hcrtr 2)-mutated narcoleptic Dobermans, we have previously demonstrated that altered dopamine (DA) D2/3 receptor mechanisms in mesencephalic DA nuclei are important for the induction of cataplexy. In the current study, we also found that the administration of D2/3 agonists into diencephalic dopaminergic cell groups, including the area dorsal to the ventral tegmental area (DRVTA) and the periventricular gray (PVG) matter of the caudal thalamus (corresponding to area A11), significantly aggravated cataplexy in hcrtr 2-mutated narcoleptic Dobermans. A D1 agonist and antagonist and a DA uptake inhibitor perfused into the DRVTA had no effect on cataplexy, suggesting an involvement of D2/3 receptors located on DA cell bodies (i.e., autoreceptors) for the regulation of cataplexy. Because the A11 cell group projects to the spinal ventral horn, the A11 D2/3 receptive mechanisms may directly modulate the activity of spinal motoneurons and modulate cataplexy.

Background: Recently, bean ferritin has been attracting considerable attention as a new source of iron, that is available to vegetarians. Although high rates of iron absorption and bioavailability from this protein have been reported, clinical data on its efficacy remain scarce. Objective: In this study, we administered bean ferritin iron to premenopausal Japanese women for nine weeks, starting immediately after menstruation, to evaluate their recovery from low hemoglobin levels as one sign of anemia. Methods: Participants in the test supplement group received an iron intake of 5 mg from one capsule containing bean extract (SloIron®) for five weeks, which was increased to 10 mg (i.e., two capsules) from the 6th to the 9th week. The study evaluated the change in hemoglobin levels as the primary endpoint, and hematocrit, red blood cell count, serum iron, MCH (mean corpuscular hemoglobin), MCHC (mean corpuscular hemoglobin concentration), serum ferritin, TSAT (TIBC), serum zinc, serum copper, anemia symptoms questionnaire, OSA sleep inventory, and the anti-fatigue questionnaire as the secondary endpoints. Results: Our results showed a significant difference (P=0.03) in the change in hemoglobin levels between the groups after nine weeks of intake, confirming the restorative effect of bean ferritin on low hemoglobin levels caused by menstruation. Moreover, a significant difference (P=0.01) was observed in the amount of change in MCHC between the two groups after five weeks of intake, and after nine weeks of intake, a significant difference in the change in both MCH (P=0.02) and MCHC P<0.01) was observed between the groups. A significant difference (P=0.03) was observed in the change in serum ferritin levels after nine weeks of intake. Conclusion: The study confirmed that iron supplementation from bean ferritin is an effective treatment for low hemoglobin and low ferritin levels caused by menstruation. [ABSTRACT FROM AUTHOR]

We designed and synthesized a series of N,N-disubstituted allylic amine type aminophosphines 2, 3 and 4, which are derivatives of chiral ligands 1. Aminophosphines 2-4 (except 2a) exist in C(aryl)- N(amine) bond axial chirality by chiral HPLC analysis. Both enantiomeric isomers of 4b were successfully obtained in an enantiomerically pure form. We demonstrated that 1a, 1b, and 4b can be used as effective chiral ligands for the palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with malonates in high enantioselectivities (up to 90% ee). [ABSTRACT FROM AUTHOR]

Unprecedented absolute asymmetric synthesis was carried out using frozen chirality derived from chiral crystals of achiral coumarin-3-carboxamide and carbenoids. An enantioselective cycloaddition reaction with a sulfur ylide gave an optically active cyclopropane up to 97% ee. Furthermore, a cycloaddition reaction with dichlorocarbene gave dihydrofuran in 93% ee. Nucleophilic addition of ylide or carbene occurs from the side of the carbonyl oxygen atom to avoid steric hindrance of substituents on the nitrogen atom. [ABSTRACT FROM AUTHOR]

Leflunomide is a disease-modifying antirheumatic drug that inhibits paw swelling and joint destruction in type II collagen-induced arthritis in mice and it also delays disease progression in patients with rheumatoid arthritis (RA), through inhibiting proliferation and cytokine production of T cells, via the blocking of de-novo pyrimidine biosynthesis by its active metabolite, A771726. However, the direct action of leflunomide on cells of osteoclast lineage responsible for bone destruction in RA remains to be clarified. In this study, we examined the effect of A771726 on osteoclast formation and bone-resorbing activity in vitro, using cultures of bone marrow-derived osteoclast progenitors and purified functionally mature osteoclasts, and then we elucidated the molecular mechanism of action of the effect of A771726 on osteoclasts. A771726 inhibited osteoclast formation from macrophage colony-stimulating factor (M-CSF)-dependent osteoclast progenitors in the presence of receptor activator of nuclear factor kappa B (NF-?B) ligand (RANKL), without any other types of cells present, in a dose-related manner, similar to the inhibition in cultures of unfractionated bone marrow cells. In addition, A771726 suppressed bone resorption by isolated mature osteoclasts. These results indicate that A771726 directly and intrinsically inhibited the differentiation and function of osteoclast lineage cells without any mediation by other cells. The inhibition by A771726 was not restored by the simultaneous addition of uridine, and may be independent of the blockade of NF-?B activation and the tyrosine phosphorylation of proteins. Thus, leflunomide, through its active metabolite, has the potential to prevent bone loss by directly inhibiting osteoclastogenesis and osteoclast function. This inhibition suggests a novel mechanism for leflunomide in the retardation of the joint destruction observed in RA patients. [ABSTRACT FROM AUTHOR]

Abstract  A 78-year-old man was admitted to Kumamoto Rosai Hospital with right lower abdominal pain. Abdominal computed tomography (CT) showed penetration of the cecum by a foreign body, which looked like a fish bone, as well as thickening of the right lower abdominal wall. We made an initial diagnosis of penetration of the colon by an ingested fish bone and the patient was managed conservatively with fasting, peripheral parental nutrition, and intravenous antibiotics. By the next day, the right lower abdominal pain had diminished and a repeat CT scan showed that the fish bone had moved to the splenic flexure. However, 2 days later, the patient complained of pain in the left upper abdomen and another CT scan showed repeated penetration of the descending colon by the same fish bone. Thus, we removed the fish bone via endoscopic extirpation. The patient had an uneventful postoperative course and was discharged home 6 days later. [ABSTRACT FROM AUTHOR]