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Most G protein-coupled receptors (GPCRs) signal through both heterotrimeric G proteins and ß-arrestins (ßarr1 and ßarr2). Although synthetic ligands can elicit biased signaling by G protein- vis-à-vis ßarr-mediated transduction, endogenous mechanisms for biasing signaling remain elusive. Here we report that S-nitrosylation of a novel site within ßarr1/2 provides a general mechanism to bias ligand-induced signaling through GPCRs by selectively inhibiting ßarr-mediated transduction. Concomitantly, S-nitrosylation endows cytosolic ßarrs with receptor-independent function. Enhanced ßarr S-nitrosylation characterizes inflammation and aging as well as human and murine heart failure. In genetically engineered mice lacking ßarr2-Cys253 S-nitrosylation, heart failure is exacerbated in association with greatly compromised ß-adrenergic chronotropy and inotropy, reflecting ßarr-biased transduction and ß-adrenergic receptor downregulation. Thus, S-nitrosylation regulates ßarr function and, thereby, biases transduction through GPCRs, demonstrating a novel role for nitric oxide in cellular signaling with potentially broad implications for patho/physiological GPCR function, including a previously unrecognized role in heart failure.
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Transdução de Sinais/fisiologia , beta-Arrestinas/metabolismo , Animais , Linhagem Celular , Regulação para Baixo/fisiologia , Feminino , Células HEK293 , Humanos , Inflamação/metabolismo , Ligantes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Células RAW 264.7 , Receptores Acoplados a Proteínas G/metabolismoRESUMO
BACKGROUND: The heart comprises many types of cells such as cardiomyocytes, endothelial cells (ECs), fibroblasts, smooth muscle cells, pericytes, and blood cells. Every cell type responds to various stressors (eg, hemodynamic overload and ischemia) and changes its properties and interrelationships among cells. To date, heart failure research has focused mainly on cardiomyocytes; however, other types of cells and their cell-to-cell interactions might also be important in the pathogenesis of heart failure. METHODS: Pressure overload was imposed on mice by transverse aortic constriction and the vascular structure of the heart was examined using a tissue transparency technique. Functional and molecular analyses including single-cell RNA sequencing were performed on the hearts of wild-type mice and EC-specific gene knockout mice. Metabolites in heart tissue were measured by capillary electrophoresis-time of flight-mass spectrometry system. The vaccine was prepared by conjugating the synthesized epitope peptides with keyhole limpet hemocyanin and administered to mice with aluminum hydroxide as an adjuvant. Tissue samples from heart failure patients were used for single-nucleus RNA sequencing to examine gene expression in ECs and perform pathway analysis in cardiomyocytes. RESULTS: Pressure overload induced the development of intricately entwined blood vessels in murine hearts, leading to the accumulation of replication stress and DNA damage in cardiac ECs. Inhibition of cell proliferation by a cyclin-dependent kinase inhibitor reduced DNA damage in ECs and ameliorated transverse aortic constriction-induced cardiac dysfunction. Single-cell RNA sequencing analysis revealed upregulation of Igfbp7 (insulin-like growth factor-binding protein 7) expression in the senescent ECs and downregulation of insulin signaling and oxidative phosphorylation in cardiomyocytes of murine and human failing hearts. Overexpression of Igfbp7 in the murine heart using AAV9 (adeno-associated virus serotype 9) exacerbated cardiac dysfunction, while EC-specific deletion of Igfbp7 and the vaccine targeting Igfbp7 ameliorated cardiac dysfunction with increased oxidative phosphorylation in cardiomyocytes under pressure overload. CONCLUSIONS: Igfbp7 produced by senescent ECs causes cardiac dysfunction and vaccine therapy targeting Igfbp7 may be useful to prevent the development of heart failure.
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Insuficiência Cardíaca , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Camundongos Knockout , Animais , Insuficiência Cardíaca/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Camundongos , Humanos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Camundongos Endogâmicos C57BL , Masculino , Modelos Animais de DoençasRESUMO
The generation of current-induced torques through the spin Hall effect in Pt has been key to the development of spintronics. In prototypical ferromagnetic-metal/Pt devices, the characteristic length of the torque generation is known to be about 1 nm due to the short spin diffusion length of Pt. Here, we report the observation of a long-range current-induced torque in Ni/Pt bilayers. We demonstrate that when Ni is used as the ferromagnetic layer, the torque efficiency increases with the Pt thickness, even when it exceeds 10 nm. The torque efficiency is also enhanced by increasing the Ni thickness, providing evidence that the observed torque cannot be attributed to the spin Hall effect in the Pt layer. These findings, coupled with our semirealistic tight-binding calculations of the current-induced torque, suggest the possibility that the observed long-range torque is dominated by the orbital Hall effect in the Pt layer.
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Diabetic nephropathy remains the leading cause of end-stage kidney disease in many countries, and additional therapeutic targets are needed to prevent its development and progression. Some angiogenic factors are involved in the pathogenesis of diabetic nephropathy. Vasohibin-2 (VASH2) is a novel proangiogenic factor, and our previous study showed that glomerular damage is inhibited in diabetic Vash2 homozygous knockout mice. Therefore, we established a VASH2-targeting peptide vaccine as a tool for anti-VASH2 therapy in diabetic nephropathy. In this study, the preventive effects of the VASH2-targeting peptide vaccine against glomerular injury were examined in a streptozotocin (STZ)-induced diabetic mouse model. The mice were subcutaneously injected with the vaccine at two doses 2 wk apart and then intraperitoneally injected with 50 mg/kg STZ for 5 consecutive days. Glomerular injury was evaluated 20 wk after the first vaccination. Treatment with the VASH2-targeting peptide vaccine successfully induced circulating anti-VASH2 antibody without inflammation in major organs. Although the vaccination did not affect blood glucose levels, it significantly prevented hyperglycemia-induced increases in urinary albumin excretion and glomerular volume. The vaccination did not affect increased VASH2 expression but significantly inhibited renal angiopoietin-2 (Angpt2) expression in the diabetic mice. Furthermore, it significantly prevented glomerular macrophage infiltration. The preventive effects of vaccination on glomerular injury were also confirmed in db/db mice. Taken together, the results of this study suggest that the VASH2-targeting peptide vaccine may prevent diabetic glomerular injury in mice by inhibiting Angpt2-mediated microinflammation.NEW & NOTEWORTHY This study demonstrated preventive effects of VASH2-targeting peptide vaccine therapy on albuminuria and glomerular microinflammation in STZ-induced diabetic mouse model by inhibiting renal Angpt2 expression. The vaccination was also effective in db/db mice. The results highlight the importance of VASH2 in the pathogenesis of early-stage diabetic nephropathy and the practicability of anti-VASH2 strategy as a vaccine therapy.
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Diabetes Mellitus Experimental , Nefropatias Diabéticas , Vacinas de Subunidades Antigênicas , Animais , Nefropatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/imunologia , Masculino , Vacinas de Subunidades Antigênicas/farmacologia , Vacinas de Subunidades Antigênicas/imunologia , Albuminúria/prevenção & controle , Camundongos Endogâmicos C57BL , Angiopoietina-2/metabolismo , Camundongos , Glomérulos Renais/patologia , Glomérulos Renais/metabolismo , Glomérulos Renais/imunologia , Proteínas Angiogênicas/metabolismo , Vacinas de Subunidades ProteicasRESUMO
Predicting the whole process of a chemical reaction while solving kinetic equations presents an opportunity to realize an on-the-fly kinetic simulation that directly discovers chemical reactions with their product yields. Such a simulation avoids the combinatorial explosion of reaction patterns to be examined by narrowing the search space based on the kinetic analysis of the reaction path network, and would open a new paradigm beyond the conventional two-step approach, which requires a reaction path network prior to performing a kinetic simulation. The authors addressed this issue and developed a practical method by combining the artificial force induced reaction method with the rate constant matrix contraction method. Two algorithms are available for this purpose: a forward mode with reactants as the input and a backward mode with products as the input. This article first numerically verifies these modes for known reactions and then demonstrates their application to the actual reaction discovery. Finally, the challenges of this method and the prospects for ab initio reaction discovery are discussed.
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INTRODUCTION: Trabecular bone score (TBS) is partially independent of fracture risk. Reference values for TBS have not been established in official guidelines, and thus clinicians often have difficulty interpreting TBS results. This study aimed to investigate whether reference values for TBS could be a valid indicator for clinical vertebral fracture (CVF). MATERIALS AND METHODS: This cross-sectional study involved 231 women with CVF and 563 women without CVF aged 60-90 years who underwent dual-energy X-ray absorptiometry during 2019-2023. They were divided into osteoporosis, osteopenia, and normal groups according to bone mineral density of the lumbar spine. Reference values for TBS were defined as low (≤ 1.23), intermediate (1.23-1.31), and high (≥ 1.31). RESULTS: Among patients without anti-osteoporosis treatment (n = 476), the proportion with low TBS was 36.7% in the CVF group and 10.7% in the control group. The proportion with CVF was higher in the low TBS group than in the intermediate and high TBS groups, especially in the osteoporosis group (p < 0.001). The odds ratio for CVF was higher in the low TBS group than in the intermediate and high especially in patients with normal BMD and osteoporosis. The TBS cut-off values for incidence of CVF in the osteoporosis, osteopenia, and normal groups were 1.224, 1.319, and 1.322, respectively. CONCLUSIONS: The reference value for low TBS (≤ 1.23) was useful as an indicator for CVF, especially in patients with osteoporosis. It is expected that reference values for TBS will be established in official guidelines in the future.
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Osteoporose , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Feminino , Fraturas da Coluna Vertebral/epidemiologia , Estudos Transversais , Valores de Referência , Osso Esponjoso , Osteoporose/diagnóstico por imagem , Osteoporose/complicações , Densidade Óssea , Absorciometria de Fóton , Vértebras Lombares/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologiaRESUMO
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are major genetic polycystic kidney diseases that can progress to end-stage kidney disease (ESKD). Longitudinal data on the clinical characteristics associated with clinical outcomes in polycystic kidney disease (PKD), including the development of ESKD and cardiovascular disease (CVD) are lacking in Japan. To address this unmet need the authors are establishing a novel, web-based, Nationwide Cohort Registry Study-the Japanese Registry of PKD (JRP). METHODS: The JRP is a prospective cohort study for ADPKD (aim to recruit n = 1000 patients), and both a retrospective and prospective study for ARPKD (aim to recruit n = 100). In the prospective registry, patients will be followed-up for 10 years every 6 months and 12 months for patients with ADPKD and ARPKD, respectively. Data collection will be recorded on Research Electronic Data Capture (REDCap) starting on April 1, 2024, with recruitment ending on March 31, 2029. (jRCT 1030230618). RESULTS: Data to be collected include: baseline data, demographics, diagnostic and genetic information, radiological and laboratory findings, and therapeutic interventions. During follow-up, clinical events such as development of ESKD, hospitalization, occurrence of extra kidney complications including CVD events, and death will be recorded, as well as patient-reported health-related quality of life for patients with ADPKD. CONCLUSIONS: The JRP is the first nationwide registry study for patients with ADPKD and ARPKD in Japan, providing researchers with opportunities to advance knowledge and treatments for ADPKD and ARPKD, and to inform disease management and future clinical practice.
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OBJECTIVE: To evaluate the preoperative haemoglobin, albumin, lymphocyte, and platelet score as a prognostic indicator in oral squamous cell carcinoma treated by radical surgery. SUBJECTS AND METHODS: Patients (83 men, 32 women; 65.80 ± 11.47 years) who underwent radical surgery between 2012 and 2022 were included. Factors affecting overall survival and disease-free survival according to the haemoglobin, albumin, lymphocyte, and platelet score were examined. Patients were categorised into low- and high-score groups using optimal cut-off values obtained from receiver operating characteristic curve analysis. RESULTS: The low-score group had poorer overall and disease-free survival (p < 0.001 each). Multivariate analysis identified alcohol consumption (hazard ratio [HR], 3.83; 95% confidence interval [CI]: 1.56-9.41, p = 0.003); vascular invasion (HR, 3.97; 95% CI: 1.60-9.85, p = 0.003); and the haemoglobin, albumin, lymphocyte, and platelet score (HR, 0.39; 95% CI: 0.20-0.78, p = 0.007) as independent prognostic factors for overall survival and vascular (HR, 3.66; 95% CI: 1.79-7.50, p < 0.001) and lymphovascular (HR, 2.44; 95% CI: 1.36-4.41, p = 0.003) invasion as independent prognostic factors for disease-free survival. CONCLUSION: The preoperative haemoglobin, albumin, lymphocyte, and platelet score may be a significant prognostic factor for patients with oral squamous cell carcinoma undergoing radical surgery.
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BACKGROUND: Oral food processing is an important part of daily food intake. A major part of this process is mastication, which prepares a bolus of food for swallowing by mechanically crushing and grinding ingested food between the teeth using rhythmic movements. Masticatory dysfunction is common in the elderly and in some neurological disorders and can have serious negative health consequences. OBJECTIVE: This study investigated the effect of restricted mastication, achieved by experimentally reducing the duration of mastication, on masticatory patterns and subsequent swallowing function. METHODS: Thirty healthy men (25 ± 3 years old) were instructed to chew gum jelly with a free mastication duration (G100), a half and a quarter duration of G100. Masseter and digastric electromyographic (EMG) activity was recorded to assess mastication and swallowing activity, respectively. In addition, the acceleration of the thyroid cartilage ridge was measured with an accelerometer. The root mean square (RMS) of muscle EMG activity in the masseter and digastric muscles, the number of masseter EMG bursts, time to peak and total duration of each masseter EMG burst, swallowing duration and laryngeal elevation latency were analysed. RESULTS: Restricting masticatory duration reduced the number of mastication cycles (p < .001), prolonged the time to peak (p < .001) and total duration of masseter EMG bursts (p < .001) and resulted in an overall increased RMS score of masseter muscle activity (p = .017). Furthermore, restricted masticatory duration led to a decrease in both swallowing duration (p = .001) and laryngeal elevation latency (p = .012), with a significant increase in the RMS score of digastric muscle activity (p < .001). CONCLUSIONS: Under the experimental conditions of restricted mastication, several adaptation features were observed, including changes in masticatory cycle characteristics and swallowing duration. Thus, although the overall masticatory efficiency was reduced, these adaptations allowed healthy individuals to still swallow safely.
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BACKGROUND: Although stimulation of Wnt/ß-catenin signaling is an important strategy to treat ischemic stroke, its signaling pathway has not been fully clarified yet. Recently, RSPO3 (R-spondin 3)/LGR4 (leucine-rich repeat-containing G protein-coupled receptor 4) signaling has resolved TLR4 (toll-like receptor 4)-induced inflammation in lung injury; however, whether this signal is critical in the ischemic brain remains unknown. Therefore, we investigated the role of RSPO3/LGR4 signaling in the ischemic brain. METHODS: BALB/c mice were exposed to permanent distal middle cerebral artery and common carotid artery occlusion. Temporal RSPO3 and LGR4 expressions were examined, and the mice were randomly assigned to receive vehicle or recombinant RSPO3. The underlying mechanisms were investigated using microglial cell lines and primary mixed glia-endothelia-neuron and primary neuronal cultures. RESULTS: In the ischemic brain, RSPO3 and LGR4 were expressed in endothelial cells and microglia/macrophages and neurons, respectively. Stimulation of RSPO3/LGR4 signaling by recombinant RSPO3 recovered neurological deficits with decreased Il1ß and iNOS mRNA on day 3 and increased Gap43 on day 9. In cultured cells, LGR4 was expressed in neuron and microglia, whereas RSPO3 promoted nuclear translocation of ß-catenin. Neuroprotective effects with reduced expression of inflammatory cytokines were observed in lipopolysaccharide-stimulated glia-endothelium-neuron cultures but not in glutamate-, CoCl2-, H2O2-, or oxygen glucose deprivation-stimulated neuronal cultures, indicating that RSPO3/LGR4 can protect neurons by regulating inflammatory cytokines. LGR4-Fc chimera, which was used to block endogenous RSPO3/LGR4 signaling, increased LPS-induced production of inflammatory cytokines, suggesting that endogenous RSPO3 suppresses inflammation. RSPO3 decreased TLR4-related inflammatory cytokine expression by decreasing TLR4 expression without affecting the M1/M2 phenotype. RSPO3 also inhibited TLR2- and TLR9-induced inflammation but not TLR7-induced inflammation, and promoted neurite outgrowth. CONCLUSIONS: RSPO3/LGR4 signaling plays a critical role in regulating TLR-induced inflammation and neurite outgrowth in the ischemic brain. Enhancing this signal will be a promising approach for treating ischemic stroke.
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AVC Isquêmico , beta Catenina , Animais , Camundongos , beta Catenina/genética , beta Catenina/metabolismo , Encéfalo/metabolismo , Citocinas/metabolismo , Células Endoteliais/metabolismo , Peróxido de Hidrogênio , Inflamação , Leucina , Crescimento Neuronal , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismoRESUMO
INTRODUCTION: Furosemide, a loop diuretic, is often empirically used to treat acute decompensated heart failure (ADHF) initially. Conversely, decongestion using tolvaptan, an aquaretic, is thought to maintain renal function compared to furosemide. However, it has not been investigated in patients with advanced chronic kidney disease (CKD) at high risk of developing acute kidney injury (AKI). This study aimed to investigate AKI incidence using tolvaptan add-on treatment, compared to increased furosemide treatment for patients with ADHF complicated by advanced CKD. METHODS: We retrospectively studied patients with advanced CKD (estimated glomerular filtration rate [eGFR] <45 mL/min/1.73 m2) who developed ADHF under outpatient furosemide treatment. The exposure was set to tolvaptan add-on treatment, and the control was set to increased furosemide treatment. RESULTS: Of the 163 patients enrolled, 79 were in the tolvaptan group and 84 in the furosemide group. The mean age was 71.6 years, the percentage of males was 63.8%, the mean eGFR was 15.7 mL/min/1.73 m2, and patients with CKD stage G5 were 61.9%. AKI incidence was 17.7% in the tolvaptan group and 42.9% in the furosemide group (odds ratio [95% confidence interval]: 0.34 [0.13-0.86], p = 0.023 in multivariate logistic regression analysis). Persistent AKI incidence was 11.8% in the tolvaptan group and 32.9% in the furosemide group (odds ratio [95% confidence interval]: 0.34 [0.10-1.06], p = 0.066 in the multinomial logit analysis). CONCLUSION: This study suggests that tolvaptan may be better than furosemide in patients with ADHF experiencing complicated advanced CKD.
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Injúria Renal Aguda , Insuficiência Cardíaca , Insuficiência Renal Crônica , Masculino , Humanos , Idoso , Tolvaptan/efeitos adversos , Furosemida/efeitos adversos , Antagonistas dos Receptores de Hormônios Antidiuréticos/efeitos adversos , Estudos Retrospectivos , Benzazepinas , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/induzido quimicamente , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/induzido quimicamente , Doença AgudaRESUMO
BACKGROUND: Clinical practice guidelines recommend antihypertensive and tolvaptan therapies for patients with autosomal dominant polycystic kidney disease (ADPKD) in Japan. However, tolvaptan therapy may pose an economic burden. The Japanese Ministry of Health, Labour and Welfare supports patients with intractable diseases. This study aimed to confirm the impact of the intractable disease system in Japan on the clinical treatment of ADPKD. METHODS: We analyzed the data of 3768 patients with ADPKD having a medical subsidy certificate from the Japanese Ministry of Health, Labour and Welfare in 2015-2016. The following quality indicators were use: the adherence rate to the 2014 clinical practice guideline for polycystic kidney disease (prescription rates of antihypertensive agents and tolvaptan in this cohort) and the number of Japanese patients with ADPKD nationwide started on renal replacement therapy in 2014 and 2020. RESULTS: Compared with new applications from 2015 to 2016, the prescription rates of antihypertensives and tolvaptan for the indicated patients at the 2017 renewal application increased by 2.0% (odds ratio = 1.41, p = 0.008) and 47.4% (odds ratio = 10.1, p > 0.001), respectively. These quality indicators improved with antihypertensive treatment, especially in patients with chronic kidney disease stages 1-2 (odds ratio = 1.79, p = 0.013) and in those aged < 50 years (odds ratio = 1.70, p = 0.003). The number of patients with ADPKD who were started on renal replacement therapy in Japan decreased from 999 in 2014 to 884 in 2020 in the nationwide database (odds ratio = 0.83, p < 0.001). CONCLUSIONS: The Japanese public intractable disease support system contributes to improvement of ADPKD treatment.
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Rim Policístico Autossômico Dominante , Humanos , Tolvaptan/uso terapêutico , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/tratamento farmacológico , Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Japão/epidemiologia , Anti-Hipertensivos/uso terapêutico , Sistema de RegistrosRESUMO
OBJECTIVES: To investigate the prognostic impact of preoperative Geriatric Nutritional Risk Index (GNRI) values in older adults undergoing radical surgery for oral squamous cell carcinoma (OSCC). SUBJECTS AND METHODS: This retrospective study included 61 patients ≥65 years old with OSCC (43 men, 18 women; age: 72.1 ± 5.4 years) who underwent radical surgery between 2013 and 2020. Factors influencing overall survival (OS) and disease-free survival (DFS) were examined. RESULTS: Receiver operating characteristic curve analysis indicated that the optimal GNRI value for classifying patients into low-GNRI (<93.7; OS: n = 19 [31.1%], DFS: n = 42 [68.9%]) and high-GNRI groups (≥93.7; OS, n = 19 [31.1%]; DFS, n = 42 [68.9%]) was 93.7. OS and DFS rates were significantly lower in the low-GNRI group than in the high-GNRI group. Univariate analysis indicated that alcohol use, preoperative serum C-reactive protein level, lymphatic invasion, postoperative treatment, and GNRI were significantly correlated with OS, while lymphatic invasion, postoperative treatment, and GNRI were significantly correlated with DFS. In multivariate analysis, only GNRI was significantly correlated with OS. DFS and postoperative treatment were independent predictors of DFS. CONCLUSIONS: Preoperative GNRI may be a significant prognostic factor in older adults with OSCC. GNRI assessment and nutritional intervention may improve prognosis in patients at high nutritional risk.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Masculino , Humanos , Feminino , Idoso , Carcinoma de Células Escamosas/cirurgia , Prognóstico , Estado Nutricional , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Avaliação Nutricional , Fatores de Risco , Neoplasias Bucais/cirurgiaRESUMO
OBJECTIVES: Nutritional status is a useful prognostic factor in gastric cancer patients. Since oral hypofunction may cause undernutrition, we cross-sectionally investigated whether the Geriatric Nutritional Risk Index (GNRI) is affected by the number of remaining teeth, occlusal support status and denture use. MATERIALS AND METHODS: The participants were 114 patients diagnosed with gastric cancer between April 2017 and March 2020. The stage of gastric cancer, body mass index, albumin level, total lymphocyte count, C-reactive protein level and GNRI were evaluated. The number of remaining teeth was also evaluated, and the occlusion state was determined based on the Eichner classification. The patients were divided into three main groups representing different occlusal states based on the Eichner index and were also categorised based on denture use. RESULTS: The mean age ± standard deviation of the patients was 75.2 ± 5.5 years. The Eichner classification had a significant positive correlation with GNRI. Low GNRI was associated with a poor occlusal state in group C, while a higher GNRI was associated with a stable occlusal state in group A. However, the denture-related groups showed no significant differences in GNRI. CONCLUSION: The GNRI was associated with the occlusal support level but not with denture use.
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Desnutrição , Neoplasias Gástricas , Humanos , Idoso , Avaliação Nutricional , Neoplasias Gástricas/complicações , Estado Nutricional , Desnutrição/etiologia , Índice de Massa Corporal , Prognóstico , Fatores de Risco , Estudos RetrospectivosRESUMO
OBJECTIVES: This study aimed to clarify the relationship between the oral assessment guide (OAG), a simple method for assessing oral function and poor nutrition in gastric cancer patients and investigate the reduction of oral mucositis through appropriate oral function management. SUBJECTS AND METHODS: Gastric cancer patients who underwent chemotherapy at the Nagoya Ekisaikai Hospital between January 2015 and December 2020 were evaluated. The prognostic nutritional index (PNI), as the objective variable, was used to assess nutritional status. The explanatory variables were sex, age, smoking status, body mass index (BMI), number of remaining teeth, cancer stage, albumin level, C-reactive protein level, white blood cell count and the OAG score. RESULTS: PNI was significantly associated with age, number of remaining teeth, cancer stage and the OAG score (p < 0.05) among the 217 patients. There were significant differences in age, BMI, cancer stage and the OAG score among the patients. An abnormal BMI and an advanced cancer stage were more common in older patients, and abnormal OAG scores were associated with a lower PNI. CONCLUSIONS: For gastric cancer patients undergoing postoperative chemotherapy, worse oral functional status is associated with worse PNI and nutritional status.
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Estado Nutricional , Neoplasias Gástricas , Humanos , Idoso , Neoplasias Gástricas/complicações , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Prognóstico , Estudos Retrospectivos , Avaliação NutricionalRESUMO
BACKGROUND: Intraoperative sinus arrest is rarely seen during zygomatic fracture treatment. The patient was diagnosed with sick sinus syndrome based on repeated postoperative sinus arrest, which could have resulted in death if diagnosed late, making this case very significant to report. CASE PRESENTATION: Sick sinus syndrome is an arrhythmia associated with reduced automaticity of the sinoatrial node or impaired sinoatrial node conduction. We report the case of a 67-year-old man diagnosed with the syndrome after a sinus arrest that occurred during a zygomatic fracture treatment. The patient had cheek pain and mouth opening disorder, dizziness after fainting and sustaining a facial injury. Preoperative examination determined that the syncope was due to drug-induced arrhythmia, and surgery was authorized after drug withdrawal. During the operation, sinus arrest was observed due to trigeminal vagal reflex, and heart rate was restarted by stopping the operation and chest compressions. After the surgery, the patient showed symptoms of dizziness and palpitations, and sinus arrest following atrial fibrillation and supraventricular tachycardia, which was diagnosed as sick sinus syndrome, and a pacemaker was implanted. Currently, 8 years have passed since the surgery, and there are no symptoms of mouth opening disorder, dizziness, or palpitations. CONCLUSIONS: In the case of maxillofacial injuries due to syncope, cardiogenic syncope is a possibility, and repeated syncope is a risk for death due to delayed diagnosis. There are no reports of maxillofacial trauma leading to a diagnosis of sick sinus syndrome. The purpose of this case report is to disseminate the importance of diagnosing the cause of syncope as well as injury treatment.
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Fibrilação Atrial , Fraturas Zigomáticas , Masculino , Humanos , Idoso , Síndrome do Nó Sinusal/terapia , Tontura , Síncope/etiologiaRESUMO
A 79-year-old male patient underwent esophagogastroduodenoscopy, which revealed a reddish lesion, 10mm in diameter, presenting as a surface recess in the angular incisure. He was diagnosed with gastric follicular lymphoma. Positron emission tomography-computed tomography revealed metastasis to the mediastinal lymph node, although the tumor size was small. Hence, we did not administer any treatment and continued following up. After 8 months, multiple enlarged lymphoma lesions in the stomach and a mass with ulceration on the oral side of the duodenal papilla were observed. The tumor had transformed into diffuse large B-cell lymphoma; therefore, chemotherapy was initiated. The patient has remained recurrence-free for 55 months after treatment.
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Linfoma Folicular , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Masculino , Humanos , Idoso , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/tratamento farmacológico , Linfoma não Hodgkin/patologia , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Estômago/patologiaRESUMO
Systematic reaction path exploration revealed the entire mechanism of Knowles's light-promoted catalytic intramolecular hydroamination. Bond formation/cleavage competes with single electron transfer (SET) between the catalyst and substrate. These processes are described by adiabatic processes through transition states in an electronic state and non-radiative transitions through the seam of crossings (SX) between different electronic states. This study determined the energetically favorable SET path by introducing a practical computational model representing SET as non-adiabatic transitions via SXs between substrate's potential energy surfaces for different charge states adjusted based on the catalyst's redox potential. Calculations showed that the reduction and proton shuttle process proceeded concertedly. Also, the relative importance of SET paths (giving the product and leading back to the reactant) varies depending on the catalyst's redox potential, affecting the yield.
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[1.1.1]Propellane, which is structurally simple and compact, exhibits promising potential for the synthesis of disubstituted straight-shaped bicyclo[1.1.1]pentane (BCP) compounds by manipulation of its highly reactive internal C-C bond. BCPs are considered to be isosteres of 1,4-disubstituted benzenes, which have found broad applications in the areas of functional molecules and drug discovery. The internal C-C single bond of [1.1.1]propellane is regarded as a charge-shift bond, which can be readily cleaved by radical means to construct BCPs. We herein report a novel synthetic method for (un)symmetric diphosphines based on the BCP motif, which can be interpreted as isosteres of 1,4-bis(diphenylphosphino)benzenes. The obtained BCP-diphosphine derivatives were used to generate a straight-shaped Au complex and an Eu-based coordination polymer.
RESUMO
The dearomative dicarboxylation of stable heteroaromatics using CO2 is highly challenging but represents a very powerful method for producing synthetically useful dicarboxylic acids, which can potentially be employed as intermediates of biologically active molecules such as natural products and drug leads. However, these types of transformations are still underdeveloped, and concise methodologies with high efficiency (e.g., high yield and high selectivity for dicarboxylations) have not been reported. We herein describe a new electrochemical protocol using the CO2 radical anion (E1/2 of CO2 = -2.2 V in DMF and -2.3 V in CH3CN vs SCE) that produces unprecedented trans-oriented 2,3-dicarboxylic acids from N-Ac-, Boc-, and Ph-protected indoles that exhibit highly negative reduction potentials (-2.50 to -2.94 V). On the basis of the calculated reduction potentials, N-protected indoles with reduction potentials up to -3 V smoothly undergo the desired dicarboxylation. Other heteroaromatics, including benzofuran, benzothiophene, electron-deficient furans, thiophenes, 1,3-diphenylisobenzofuran, and N-Boc-pyrazole, also exhibit reduction potentials more positive than -3 V and served as effective substrates for such dicarboxylations. The dicarboxylated products thus obtained can be derivatized into useful synthetic intermediates for biologically active compounds in few steps. We also show how the dearomative monocarboxylation can be achieved selectively by choice of the electrolyte, solvent, and protic additive; this strategy was then applied to the synthesis of an octahydroindole-2-carboxylic acid (Oic) derivative, which is a useful proline analogue.