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Although nirmatrelvir/ritonavir (NMV/r) reportedly increases blood levels of tacrolimus (TAC) due to CYP3A4 inhibition and other factors, reports on the use of NMV/r in combination with tacrolimus hydrate extended-release capsules (TAC-ER) in lung transplant patients are limited. Herein, we present a case with post-lung transplantation of elevated blood trough levels of TAC after concomitant use of NMV/r. A woman in her 60s had undergone lung transplantation. She had coronavirus disease 2019 (COVID-19) and was co-administered NMV/r and TAC-ER, with the trough level controlled at approximately 4 µg/mL. Upon the co-administration of NMV/r and TAC-ER, the patient developed diarrhea and vomiting and was hospitalized. TAC-ER was discontinued on day 6, and TAC level was measured on day 8 and had risen above 100 ng/mL. This level gradually decreased to 17.8 ng/mL on day 11 and 2.4 ng/mL on day 15; therefore, TAC-ER was resumed at 2.5 mg/day. On day 18, the TAC level was 5.2 ng/mL, which was within the target range, and the patient was discharged on day 19. This is the first report of a post-lung transplant patient co-administered TAC-ER with NMV/r, who showed abnormally high blood TAC levels above the detection limit. In patients using TAC-ER after lung transplantation, it may be useful to confirm that the TAC blood level is below the effective therapeutic range before resuming TAC-ER safely.
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Urothelial carcinoma of the bladder with osteoclast-like giant cells (UCOGCs) is rare among the subtypes of poorly differentiated urothelial carcinoma. Its clinical significance and optimal treatment are unknown, and few reports on genomic analysis of UCOGCs have been reported. Detailed analysis including genetic analysis for rare type variants of cancer could be a foothold for further research. The present case describes the case of a 75-year-old man who presented with a non-papillary bladder tumor 56 mm in diameter showing gross hematuria and pain on voiding. Following transurethral resection of the bladder tumor, the pathological diagnosis was invasive UCOGCs. Neoadjuvant chemotherapy and radical cystectomy were performed with the resected tumor pathologically diagnosed as invasive UCOGCs, high grade, pT3b, pN1. The present study also analyzed the genomic features using a cancer panel test. The panel test noted six gene alterations (PIK3CA p.E542K, HRAS p.G13R, ARAF copy number amplification, CDKN2A copy number loss, TP53 p.E285V, ARID1A p.S90Pfs*11) and telomerase reverse transcriptase (TERT) promoter variant. Accumulation of knowledge from molecular-based testing is anticipated to determine precise treatment for rare cancer.
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Seed longevity is a crucial trait for the seed industry and genetic resource preservation. To develop excellent cultivars with extended seed lifespans, it is important to understand the mechanism of keeping seed germinability long term and to find useful genetic resources as prospective breeding materials. This study was conducted to identify the best cultivars with a high and stable seed longevity trait in the germplasm of rice (Oryza sativa L.) and to analyze the correlation between seed longevity and embryonic RNA integrity. Seeds from 69 cultivars of the world rice core collection selected by the NIAS in Japan were harvested in different years and subjected to long-term storage or controlled deterioration treatment (CDT). The long-term storage (4 °C, RH under 35%, 10 years) was performed on seeds harvested in 2010 and 2013. The seeds harvested in 2016 and 2019 were used for CDT (36 °C, RH of 80%, 40 days). Seed longevity and embryonic RNA integrity were estimated by a decrease in the germination percentage and RNA integrity number (RIN) after long-term storage or CDT. The RIN value was obtained by the electrophoresis of the total RNA extracted from the seed embryos. Seeds of "Vandaran (indica)", "Tupa 729 (japonica)", and "Badari Dhan (indica)" consistently showed higher seed longevity and embryonic RNA integrity both under long-term storage and CDT conditions regardless of the harvest year. A strong correlation (R2 = 0.93) was observed between the germination percentages and RIN values of the seeds after the long-term storage or CDT among nine cultivars selected based on differences in their seed longevity. The study findings revealed the relationship between rice seed longevity and embryo RNA stability and suggested potential breeding materials including both japonica and indica cultivars for improving rice seed longevity.
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BACKGROUND: We investigated whether the initial voriconazole (VRCZ) dosing design, as determined using simulation software with a population pharmacokinetic model of Japanese patients, impacts the effectiveness and safety when compared with VRCZ initiation according to the package insert. METHODS: In this single-center retrospective observational study, we employed records from Tosei General Hospital (a 633-bed hospital), dated April 2017 to September 2023. Eligible patients were divided into the software-based simulation group, comprising patients administered initial VRCZ dosage adjustment by pharmacists using software-based simulation, and the standard therapy group, whose dosage was administered by a physician following the package insert recommendations without simulation. The primary objective of this study was to determine the efficacy of VRCZ first-dose design in reducing the incidence of hepatotoxicity and visual symptoms. RESULTS: The median ages of enrolled participants (n = 93) were 75 (68-79) and 72 (65-78) years in the software-based simulation and standard therapy groups, respectively. Regardless of formulation, initial trough concentrations were lower in the VRCZ software-based first dosage adjustment group and higher rate within the appropriate range (1-4 µg/mL). The incidence of all-grade hepatotoxicity or visual symptoms was significantly lower in the software-based simulation group. The log-rank test revealed a significant impact on the occurrence of ≥grade 2 hepatotoxicity in the software-based first dosage adjustment group compared to that in the standard therapy group. CONCLUSIONS: The initial VRCZ dosing design using simulation software improved the achievement of appropriate initial trough concentrations and resulted in fewer occurrences of hepatotoxicity (≥grade 2) when compared with the standard therapy.
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We demonstrate hydrothermally grown sodium hydrogen zirconium phosphate ((Na,H)-ZrP) crystals exhibiting high calcium ion selectivity. The standard Gibbs free energies for Ca2+ exchange on (Na,H)-ZrP and γ-type ZrP were estimated to be -10.1 and -4.69 kJ mol-1, respectively. The high Ca2+ selectivity of (Na,H)-ZrP could be attributed to the size matching between the ion exchange site of (Na,H)-ZrP and Ca2+.
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BACKGROUND: Recent studies have revealed that thyroid and autoimmune diseases may be associated with sporadic moyamoya disease. However, whether routine screening serum tests to detect these underlying diseases are useful or not remains unclear. METHODS: We retrospectively evaluated 459 patients with moyamoya disease but without previous history of thyroid or autoimmune diseases who underwent the screening serum tests targeting thyroid and autoimmune diseases from 2016 to 2023 in our institute. The number of patients who were diagnosed as thyroid or autoimmune diseases after these tests were investigated. RESULTS: Among the patients who were screened, 237 (42.6â¯%) patients had abnormal results for some factors, such as thyroid hormones or autoantibodies. After consultation with endocrinologists or rheumatologists, 27 (5.9â¯%) patients were newly diagnosed with thyroid diseases, including six (1.3â¯%) patients with Graves' disease, 19 (4.1â¯%) patients with Hashimoto thyroiditis and two (0.4â¯%) patients with other thyroid diseases; however, none of the patients were diagnosed with nonthyroidal autoimmune diseases, such as Sjogren's syndrome, antiphospholipid syndrome, or rheumatoid arthritis, listed as moyamoya-related diseases and targeted by our screening serum tests. Patients with newly diagnosed underlying diseases were more likely to be female compared to patients without new diagnosis (96.3â¯% vs. 72.2â¯%, p = 0.03). CONCLUSION: Routine thyroid-related serum screening may be clinically meaningful in patients with moyamoya disease to detect occult thyroid diseases, especially in female patients. However, routine serum screening tests targeting other autoimmune diseases are not recommended unless the patients have equivalent symptoms.
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Enfermedades Autoinmunes , Enfermedad de Moyamoya , Enfermedades de la Tiroides , Humanos , Enfermedad de Moyamoya/sangre , Enfermedad de Moyamoya/diagnóstico , Femenino , Masculino , Adulto , Persona de Mediana Edad , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/diagnóstico , Estudios Retrospectivos , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/sangre , Autoanticuerpos/sangre , Adulto Joven , Adolescente , Anciano , NiñoRESUMEN
BACKGROUND: Microvascular decompression (MVD), the standard surgical approach for hemifacial spasm (HFS), can be divided into the interposition and transposition methods. Although the risk of HFS recurrence following interposition has been reported, there is limited data comparing long-term outcomes between both methods performed by a single surgeon. This study aimed to investigate the efficacy of MVD techniques on HFS by comparing surgical outcomes performed by a single surgeon in a single-center setting. METHODS: A total of 109 patients who underwent MVD were analyzed and divided into the transposition (86 patients) and interposition (23 patients) groups. Postoperative outcomes at 1 month and 1 year were assessed and compared, including rates of spasm relief, complications, and recurrence. RESULTS: Outcome assessment revealed higher rates of early spasm relief in the interposition group (66.3% vs. 100%, transposition vs. interposition, respectively, p = 0.0004), although spasm relief at 1-year postoperatively was comparable between the two groups (84.9% vs. 95.7%, transposition vs. interposition, respectively, p = 0.2929). No significant differences were observed in complication and recurrence rates. Kaplan-Meier analysis demonstrated no significant differences in the duration of spasm resolution by MVD method (p = 0.4347, log-rank test). CONCLUSION: This study shows that both the transposition (Surgicel® and fibrin glue) and interposition (sponge) methods were excellent surgical techniques. The interposition method may achieve earlier spasm resolution compared to the transposition method.
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Espasmo Hemifacial , Cirugía para Descompresión Microvascular , Humanos , Espasmo Hemifacial/cirugía , Cirugía para Descompresión Microvascular/métodos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto , Anciano , Complicaciones Posoperatorias/etiología , RecurrenciaRESUMEN
Introduction: The incidence of steatotic liver disease has increased in recent years. Thus, steatotic liver disease is a major public health issue in Japan. This study investigated the association between weight reduction and the remission of metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic and alcohol related/associated liver disease (MetALD) in Japanese individuals undergoing health checkups. Methods: This retrospective observational study included 8,707 Japanese patients with MASLD/MetALD who underwent health checkups from May 2015 to March 2023. The participants were monitored for its remission at their subsequent visit. MASLD was diagnosed on abdominal ultrasonography and based on the presence of at least one of five metabolic abnormalities. The impact of body mass index (BMI) reduction on MASLD/MetALD remission was assessed via logistic regression analysis and using receiver operating characteristic curves. Results: Logistic regression analysis revealed that weight loss was significantly associated with MASLD/MetALD remission. Other factors including exercise habits and reduced alcohol consumption were significant predictors of MASLD/MetALD remission in the overall cohort and in male patients. The optimal BMI reduction cutoff values for MASLD/MetALD remission were 0.9 kg/m2 and 4.0% decrease in the overall cohort, 0.85 kg/m2 and 3.9% decrease in males, and 1.2 kg/m2 and 4.5% decrease in females. In participants with a BMI of 23 kg/m2, the cutoff values were 0.75 kg/m2 and 2.7% BMI reduction. Discussion: Weight reduction plays an important role in both MASLD and MetALD remission among Japanese individuals. That is, targeting specific BMI reduction is effective. This underscores the importance of targeted weight management strategies in preventing and managing MASLD/MetALD in the Japanese population.
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Índice de Masa Corporal , Pérdida de Peso , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Japón/epidemiología , Adulto , Hígado Graso/epidemiología , Anciano , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/etiología , Pueblos del Este de AsiaRESUMEN
Mutations in the Trk-fused gene (TFG) cause hereditary motor and sensory neuropathy with proximal dominant involvement, which reportedly has high co-incidences with diabetes and dyslipidemia, suggesting critical roles of the TFG in metabolism as well. We found that TFG expression levels in white adipose tissues (WATs) were elevated in both genetically and diet-induced obese mice and that TFG deletion in preadipocytes from the stromal vascular fraction (SVF) markedly inhibited adipogenesis. To investigate its role in vivo, we generated tamoxifen-inducible adipocyte-specific TFG knockout (AiTFG KO) mice. While a marked down-regulation of the peroxisome proliferator-activated receptor gamma target, de novo lipogenesis (DNL), and mitochondria-related gene expressions were observed in subcutaneous WAT (scWAT) from AiTFG KO mice, these effects were blunted in SVF-derived adipocytes when the TFG was deleted after differentiation into adipocytes, implying cell nonautonomous effects. Intriguingly, expressions of thyroid hormone receptors, as well as carbohydrate responsive element-binding protein ß, which mediates the metabolic actions of thyroid hormone, were drastically down-regulated in scWAT from AiTFG KO mice. Reduced DNL and thermogenic gene expressions in AiTFG KO mice might be attributable to impaired thyroid hormone action in vivo. Finally, when adipocyte TFG was deleted in either the early or the late phase of high-fat diet feeding, the former brought about an impaired expansion of epididymal WAT, whereas the latter caused prominent adipocyte cell death. TFG deletion in adipocytes markedly exacerbated hepatic steatosis in both experimental settings. Collectively, these observations indicate that the TFG plays essential roles in maintaining normal adipocyte functions, including an enlargement of adipose tissue, thyroid hormone function, and thermogenic gene expressions, and in preserving hypertrophic adipocytes.
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Aldosterone secretion in primary aldosteronism (PA) is often regulated by adrenocorticotropic hormone (ACTH) in addition to its autonomous secretion. However, the clinical characteristics and risk of cardiovascular and cerebrovascular (CCV) events in PA patients with aldosterone responsiveness to ACTH stimulation remain unclear. This study aimed to investigate the prevalence of CCV events in PA patients with high aldosterone responsiveness to ACTH stimulation. A retrospective cross-sectional study was conducted as part of the Japan Primary Aldosteronism Study/Japan Rare Intractable Adrenal Disease project. PA patients with adrenal venous sampling (AVS) between January 2006 and March 2019 were enrolled. The ACTH-stimulated plasma aldosterone concentration (PAC) of the inferior vena cava during AVS was used to evaluate aldosterone responsiveness to ACTH. We analyzed the relationship between responsiveness and previous CCV events. Logistic regression analysis demonstrated that the ΔPAC (the difference between the PAC measurements before and after ACTH stimulation) significantly increased the odds of previous CCV events in PA patients after adjusting for classical CCV event risk factors, baseline PAC and duration of hypertension (relative PAC: odds ratio [OR], 2.896; 95% confidence interval [CI], 0.989-8.482; ΔPAC: OR, 2.344; 95% CI, 1.149-4.780; ACTH-stimulated PAC: OR, 2.098; 95% CI, 0.694-6.339). This study clearly demonstrated that aldosterone responsiveness to ACTH is closely related to previous CCV events. The responsiveness of the PAC to ACTH could be useful in predicting CCV event risk.Registration Number in UMIN-CTR is UMIN000032525.
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Hormona Adrenocorticotrópica , Aldosterona , Enfermedades Cardiovasculares , Trastornos Cerebrovasculares , Hiperaldosteronismo , Humanos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/complicaciones , Hormona Adrenocorticotrópica/sangre , Aldosterona/sangre , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Estudios Retrospectivos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/sangre , Trastornos Cerebrovasculares/epidemiología , Trastornos Cerebrovasculares/sangre , Anciano , Adulto , Japón/epidemiologíaRESUMEN
PURPOSE: Low physical function can be effectively improved via intradialytic exercise. However, the association between the effects of intradialytic exercise on physical function and malnutrition severity has not been studied extensively. This study aimed to investigate the impact of nutritional status severity on physical function in patients undergoing hemodialysis with low physical function to whom intradialytic exercise was prescribed. METHODS: The participants were patients with decreased mobility [walking speed < 1.0 m/s and/or Short Physical Performance Battery (SPPB) < 12] who had been undergoing hemodialysis thrice a week for 6 months and performing intradialytic exercise program. Patients were divided into groups based on the Geriatric Nutritional Risk Index (GNRI) [Non-malnutrition group (GNRI > 98), Gentle/slim malnutrition group (GNRI ≤ 98, GNRI ≥ 92), Mild malnutrition group (GNRI < 92, GNRI ≥ 82), Severe malnutrition group (GNRI < 82)]. The primary outcomes were Grip strength, isometric knee extension strength (IKES), SPPB, and 10-m walking speed measured at baseline and at 6 months. Statistical analyses were performed using a linear mixed-effects model with the intention-to-treat analysis, including within-group analysis and between-group comparison. RESULTS: A total of 805 participants were included in the study. Within-group comparisons showed significantly improved IKES, 10-m walking speed, and SPPB improved, except in the Severe malnutrition group. Grip strength significantly improved in the Gentle/slim and mild malnutrition groups. Between-group comparison with controls showed that the improvement in Grip strength was significantly bigger in the Gentle/slim malnutrition group [0.98 (0.15 to 1.82) kg] than in the non-malnutrition group. However, IKES in the Severe malnutrition group [- 5.14 (- 9.18 to - 1.10) %] less significantly improve than that in the non-malnutrition group. No significant differences were found in the other indices. CONCLUSION: In patients with severe malnutrition, the changes in IKES scores resulting from Intradialytic exercise were significantly smaller than those observed in non-malnourished patients. Therefore, it is necessary to initiate suitable nutritional and exercise therapy based on the severity of malnutrition.
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Desnutrición , Diálisis Renal , Humanos , Masculino , Femenino , Desnutrición/etiología , Anciano , Persona de Mediana Edad , Estudios de Cohortes , Terapia por Ejercicio/métodos , Resultado del Tratamiento , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/fisiopatología , Estado Nutricional , Estudios ProspectivosRESUMEN
In endovascular therapy (EVT) for femoropopliteal artery (FPA) lesions, studies examining the relationship between lesion morphology and hemodynamic status are limited. The purpose of this study was to investigate FPA lesion characteristics, including imaging findings and their cutoff values that can predict hemodynamic significance after balloon angioplasty. This single-center retrospective study enrolled 50 de novo FPA lesions from 43 patients treated under intravascular ultrasound (IVUS) usage between June 2022 and March 2023. As a physiological parameter, the pressure gradient was measured, and the cutoff value of the residual pressure gradient (RPG) was defined as a systolic pressure > 10 mmHg through the lesions after balloon angioplasty. The pressure gradients were measured using a 0.014-inch wire-guided, rapid exchange-type microcatheter, Navvus II (Acist, Eden Prairie, Minnesota, USA). Predictive risk factors for RPG were analyzed using the random forest (RF) method. The relationship between the variables, RPG, and the cutoff points of each predictor was assessed using the partial dependence plot (PDP) method. RPG was observed in 20% of the lesions after balloon angioplasty. The RF model revealed that the percent diameter stenosis (%DS) and minimum lumen area (MLA) on IVUS assessment were strong predictive factors for RPG after balloon angioplasty. The PDP model revealed that a higher %DS (cutoff 30%) and smaller MLA (cutoff 10 mm2) could predict RPG after balloon angioplasty. Conventional lesion parameters such as %DS and MLA can predict hemodynamic significance during EVT for FPA lesions.
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Angioplastia de Balón , Arteria Femoral , Enfermedad Arterial Periférica , Arteria Poplítea , Ultrasonografía Intervencional , Humanos , Arteria Femoral/fisiopatología , Arteria Femoral/diagnóstico por imagen , Masculino , Arteria Poplítea/diagnóstico por imagen , Arteria Poplítea/fisiopatología , Femenino , Estudios Retrospectivos , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/métodos , Anciano , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/diagnóstico , Ultrasonografía Intervencional/métodos , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más Años , Grado de Desobstrucción Vascular , Factores de RiesgoRESUMEN
Bacillus pumilus TUAT1 acts as plant growth-promoting rhizobacteria for various plants like rice and Arabidopsis. Under stress conditions, B. pumilus TUAT1 forms spores with a thick peptidoglycan (PGN) cell wall. Previous research showed that spores were significantly more effective than vegetative cells in enhancing plant growth. In Arabidopsis, lysin motif proteins, LYM1, LYM3 and CERK1, are required for recognizing bacterial PGNs to mediate immunity. Here, we examined the involvement of PGN receptor proteins in the plant growth promotion (PGP) effects of B. pumilus TUAT1 using Arabidopsis mutants defective in PGN receptors. Root growth of wild-type (WT), cerk1-1, lym1-1 and lym1-2 mutant plants was significantly increased by TUAT1 inoculation, but this was not the case for lym3-1 and lym3-2 mutant plants. RNA-seq analysis revealed that the expression of a number of defense-related genes was upregulated in lym3 mutant plants. These results suggested that B. pumilus TUAT1 may act to reduce the defense response, which is dependent on a functional LYM3. The expression of the defense-responsive gene, WRKY29, was significantly induced by the elicitor flg-22, in both WT and lym3 mutant plants, while this induction was significantly reduced by treatment with B. pumilus TUAT1 and PGNs in WT, but not in lym3 mutant plants. These findings suggest that the PGNs of B. pumilus TUAT1 may be recognized by the LYM3 receptor protein, suppressing the defense response, which results in plant growth promotion in a trade-off between defense and growth.
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Proteínas de Arabidopsis , Arabidopsis , Bacillus pumilus , Regulación de la Expresión Génica de las Plantas , Peptidoglicano , Arabidopsis/genética , Arabidopsis/microbiología , Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Peptidoglicano/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Bacillus pumilus/genética , Bacillus pumilus/metabolismo , Bacillus pumilus/fisiología , Raíces de Plantas/microbiología , Raíces de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Mutación , Inmunidad de la PlantaRESUMEN
PURPOSE: Few clinical studies have compared the operative outcomes between loose- and press-fit stems in radial head arthroplasty (RHA). We aimed to evaluate the radiographic and clinical results of the two radial head implant concepts. METHODS: In this retrospective multicenter study, 32 patients (24 women and 8 men) with a mean age of 63.1 years who underwent RHA for comminuted radial head fractures were reviewed between 2005 and 2021. Seventeen patients underwent RHA with a loose-fit stem (L-group), whereas the remaining fifteen patients underwent RHA with a press-fit stem (P-group). The mean follow-up period was 40.1 ± 9.9 months, with the minimum follow-up duration of 12 months. The radiographic findings were evaluated for periprosthetic osteolysis; furthermore, clinical outcomes were analyzed to measure the range of motion of the elbow. The rate of reoperations and prosthesis removal were also reviewed. RESULTS: The general characteristics of the patients were similar in the two groups. The rate of periprosthetic osteolysis was 17.6% in the L-group, whereas it was 53.3% in the P-group. The mean elbow flexions were 128° and 133° in the L- and P-groups, respectively. The mean elbow extensions were -12° and -9° in the L- and P-groups, respectively. The rate of reoperation was 23.5% in the L-group and 15.2% in the P-group. One patient in the L-group had the prosthesis removed because of surgical site infection, whereas one patient in the P-group had the prosthesis removed owing to painful loosening. CONCLUSIONS: No significant differences in the clinical outcomes and reoperation rate were observed between the two radial head implant concepts in this study. However, osteolysis occurred more frequently in the P-group. Although patients with periprosthetic osteolysis are currently asymptomatic, they should be carefully followed up for the symptoms in the long term.
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BACKGROUND/AIM: A genomic analysis based on next-generation sequencing is important for deciding cancer treatment strategies. Cancer tissue sometimes displays intratumor heterogeneity and a pathologic specimen may contain more than two tumor grades. Although tumor grades are very important for the cancer prognosis, the impact of higher tumor grade distribution in a specimen used for a genomic analysis is unknown. PATIENTS AND METHODS: We retrospectively analyzed the data of 61 clear cell carcinoma and 46 prostate cancer patients that were diagnosed between December 2018 and August 2022 using the GeneRead Human Comprehensive Cancer Panel or SureSelect PrePool custom Tier2. Genome annotation and curation were performed using the GenomeJack software. RESULTS: Tumor mutation burden (TMB) was increased in proportion to the higher tumor grade distribution in grade 2 clear cell renal cell carcinoma (ccRCC). In PC, Grade Group 3/4 specimens that included an increased distribution of Gleason pattern 4 had more frequent gene mutations. CONCLUSION: Our results suggest the importance of selecting the maximum distribution of higher tumor grade areas to obtain results on the precise gene alterations for genomics-focused treatments.
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Carcinoma de Células Renales , Neoplasias Renales , Neoplasias de la Próstata , Masculino , Humanos , Carcinoma de Células Renales/genética , Estudios Retrospectivos , Neoplasias de la Próstata/genética , Mutación , Neoplasias Renales/genéticaRESUMEN
PURPOSE: Exercise therapy is a crucial intervention for improving health-related quality of life (HRQOL) in patients undergoing haemodialysis. However, factors that improve HRQOL by improving physical function and dialysis-related symptoms remain unknown. This study aimed to examine the physical function parameters and dialysis-related symptoms that improve HRQOL following intradialytic exercise. METHODS: This multicentre cohort study included 596 patients who participated in an intradialytic exercise program three times per week for a period of 6 months, which comprised of stretching and resistance training. EuroQol 5 dimensions 5-level (EQ5D-5L), grip strength, isometric knee extension strength, 10-m walking speed, Short Physical Performance Battery (SPPB), and improvement in dialysis-related symptoms were measured at the baseline and post-intervention. A linear mixed model was used to analyse the effects of improved physical function and dialysis-related symptoms on improvements in EQ5D-5L. RESULTS: As a physical function index affecting ΔEQ5D-5L, only SPPB showed a significant increase in ΔEQ5D-5L compared with the non-improved group [difference in ΔEQ5D-5L, 0.05 (0.004 to 0.092) point; p < 0.05]). In addition, dialysis-related symptoms with Improved physical conditions [difference in ΔEQ5D-5L, 0.07 (0.02 to 0.13) point] and an Extended walking distance [difference in ΔEQ5D-5L was 0.07 (0.01 to 0.12) point] significantly influenced ΔEQ5D-5L (p < 0.05, both). CONCLUSIONS: The improvements observed in the SPPB scores and self-percieved physical fitness and ambulation range, attributable to intradialytic exercise, may potentially improve HRQOL.
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Fallo Renal Crónico , Diálisis Renal , Humanos , Calidad de Vida/psicología , Fallo Renal Crónico/terapia , Estudios de Cohortes , Pacientes Ambulatorios , Terapia por EjercicioRESUMEN
Crystal growth methods that do not require high temperatures are highly needed for the facile growth of oxide single crystals with melting points of several thousand degrees Celsius. This paper represents the first report of a method for the low-temperature growth of ruby crystals (chromium-doped Al2O3) at 750 °C, which is one-third of the conventionally required temperature (2050 °C). In solution-based crystal growth, the target crystal is grown at a temperature considerably lower than its melting point. However, conventional crystal growth processes involving solvent evaporation and cooling require high temperatures to completely liquefy the material, with previously reported solution growth temperatures of ≈1100 °C. Supersaturation based on the decomposition of crystal-solvent intermediates eliminates the need to completely liquefy the material, enabling low-temperature crystal growth. The combination of computational and experimental investigations helps determine the optimum conditions for low-temperature crystal growth. The proposed method is a novel green process that breaks the conventional frontiers of crystal growth while ensuring eco-friendliness and low energy consumption. In addition, its scope can potentially be expanded to the synthesis of various crystals and direct growth on substrates with low melting points.
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The safety and efficacy of hemoglobin vesicles (HbVs) as artificial oxygen carriers encapsulating a purified and concentrated Hb solution in liposomes have been studied extensively. The HbV surface, modified with PEG by incorporating a PEG-conjugated phospholipid, is beneficial for storage and biocompatibility. However, it might be possible that interaction of PEG and the pre-existing anti-PEG antibody in the bloodstream causes acute adverse reaction. This study used two sets of experiments with rats and guinea pigs to ascertain whether the anti-PEG antibody generated by the PEG-modified HbV injection can induce anaphylactic reactions. SD rats received repeated intravenous injection of HbV at a dose rate of 16 or 32 mL/kg three times. Not anti-PEG IgG but anti-PEG IgM was detected. Nevertheless, no anaphylactic reaction occurred. Guinea pigs were used to study the presence of active systemic anaphylaxis further after injections of the PEG-modified liposomes used for HbV. The animals were sensitized by three repeated subcutaneous injections of PEG-modified liposomes (PEG-liposome) along with adjuvant at 1 week intervals. For comparison, unmodified liposomes (liposome) and 10 times excessively PEG-modified liposomes with ionizable lipid (10PEG-DODAP-liposome) were used. Inclusion of PEG modification induced not only anti-PEG IgM but also anti-PEG IgG. Three weeks after the final injection, intravenous injection of both PEG-liposome and liposome (1 mL/kg) induced no anaphylactic reaction. However, the injection of 10PEG-DODAP-liposome showed one lethal anaphylaxis case and one mild anaphylaxis case. Antisera obtained from the animal sensitized as described above were inoculated (0.05 mL) intradermally into fresh guinea pigs. The presence of passive cutaneous anaphylaxis was evaluated after intravenous injections (1 mL/kg) of three liposomes with Evans blue. No dye leakage was detected at any inoculated skin point for PEG-liposome or liposome, but a slight leakage was detected in one inoculated skin point for 10PEG-DODAP-liposome. These results indicate the absence of acute allergic reactions at repeated injections of HbVs despite the anti-PEG antibody induction. Not all the PEG-modified liposomes show anaphylaxis, and it may depend on the amount of PEGylated phospholipid and lipid composition of PEG-modified liposomes.