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The long survival of patients with primary cancer increases the chance of such patients developing second primary cancer (SPC). The development of SPC in cancer survivors exerts a large psychological, social and economic burden on patients and their families. The aim of the present study was to assess the risk of cancer survivors developing SPC. The study included patients who had been diagnosed with a first primary cancer in five organs (stomach, colorectum, lung, breast and thyroid), which are the five most common sites of cancer in patients from Korea, at the regional cancer center in Jeonbuk National University Hospital between January 2007 and December 2009. The standardized incidence ratio (SIR) of SPC according to sex and site was calculated from 5,209 patients who were followed up to September 2017. General incidence was acquired from the National Cancer Registry of Republic of Korea. SPC occurred in 6.2% (323/5,209) of patients, and the incidence of SPC among the five major types of cancer was in the order of breast (8.8%, 46/524), colorectum (8.6%, 86/1,003), gastric (6.6%, 89/1,358), thyroid (4.7%, 67/1,437) and lung cancer (3.9%, 35/887). When all SPC sites were included, the SIRs of SPC in patients with colorectal cancer and breast cancer were >1.0 (1.21 and 1.66, respectively). Breast cancer and thyroid cancer exhibited a high site relationship (P<0.05), and colorectal cancer had a high site relationship with gastric cancer (P<0.05). The present study analyzed the incidence and pattern of SPC in patients with cancer who were diagnosed with primary carcinoma in five organs. The results of the study may be useful for effective follow-up and early detection of SPC in patients with cancer.

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IMPORTANCE: Osteoporosis-related fractures are associated with increased mortality risk among postmenopausal women, yet the impact of antiosteoporotic medications on mortality is not fully understood. OBJECTIVE: This study evaluates the effect of antiresorptive agents (ARs) on mortality risk in postmenopausal women with osteoporosis. DESIGN: This is a nationwide cohort study using data from the National Screening Program for Transitional Ages (2008-2017). SETTING: Data were derived from a national cohort of postmenopausal women in South Korea. PARTICIPANTS: This study included 117 871 postmenopausal women diagnosed with osteoporosis. Of them, 15 895 patients who used ARs, such as bisphosphonates or selective estrogen receptor modulators, for at least 1 year were matched 1:1 with nonusers using propensity scores. EXPOSURES: Exposure to ARs for at least 1 year was compared with no AR use. MAIN OUTCOMES AND MEASURE: Mortality outcomes were assessed using multivariable Cox proportional hazard regression models, focusing on all-cause mortality and cause-specific mortality, particularly cardiovascular disease (CVD) and injury-/fracture-related deaths. RESULTS: In AR users, there were 102 deaths (mortality rate 1.41 per 1000 person-years), compared with 221 deaths in non-users (mortality rate 3.14 per 1000 person-years), yielding a hazard ratio (HR) of 0.43 (95% CI, 0.34-0.54). Antiresorptive agent users showed a 52% reduction in CVD mortality risk (HR, 0.48; 95% CI, 0.34-0.69) and a 54% reduction in injury-/fracture-related mortality risk (HR, 0.46; 95% CI, 0.27-0.76). The analysis indicated a consistent decrease in all-cause and CVD mortality risks with longer durations of AR use. CONCLUSIONS AND RELEVANCE: The use of ARs in postmenopausal women with osteoporosis is associated with significantly lower risks of all-cause mortality, especially from cardiovascular events and fractures. The mortality reduction benefits appear to be enhanced with prolonged AR therapy, highlighting the potential importance of sustained treatment in this population.

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Conservadores de la Densidad Ósea , Osteoporosis Posmenopáusica , Humanos , Femenino , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/mortalidad , Anciano , Conservadores de la Densidad Ósea/uso terapéutico , República de Corea/epidemiología , Persona de Mediana Edad , Estudios de Cohortes , Posmenopausia , Fracturas Osteoporóticas/mortalidad , Fracturas Osteoporóticas/prevención & control , Fracturas Osteoporóticas/epidemiología , Difosfonatos/uso terapéutico , Enfermedades Cardiovasculares/mortalidad , Modelos de Riesgos Proporcionales , Mortalidad/tendencias , Factores de Riesgo

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PAK4 and PD-L1 have been suggested as novel therapeutic targets in human cancers. Moreover, PAK4 has been suggested to be a molecule closely related to the immune evasion of cancers. Therefore, this study evaluated the roles of PAK4 and PD-L1 in the progression of osteosarcomas in 32 osteosarcomas and osteosarcoma cells. In human osteosarcomas, immunohistochemical positivity for the expression of PAK4 (overall survival, p = 0.028) and PD-L1 (relapse-free survival, p = 0.002) were independent indicators for the survival of patients in a multivariate analysis. In osteosarcoma cells, the overexpression of PAK4 increased proliferation and invasiveness, while the knockdown of PAK4 suppressed proliferation and invasiveness. The expression of PAK4 was associated with the expression of the molecules related to cell cycle regulation, invasion, and apoptosis. PAK4 was involved in resistance to apoptosis under a treatment regime with doxorubicin for osteosarcoma. In U2OS cells, PAK4 was involved in the stabilization of PD-L1 from ubiquitin-mediated proteasomal degradation and the in vivo infiltration of immune cells such as regulatory T cells and PD1-, CD4-, and CD8-positive cells in mice tumors. In conclusion, this study suggests that PAK4 is involved in the progression of osteosarcoma by promoting proliferation, invasion, and resistance to doxorubicin and stabilized PD-L1 from proteasomal degradation.

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Antígeno B7-H1 , Proliferación Celular , Doxorrubicina , Resistencia a Antineoplásicos , Osteosarcoma , Quinasas p21 Activadas , Osteosarcoma/patología , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/metabolismo , Osteosarcoma/genética , Humanos , Antígeno B7-H1/metabolismo , Femenino , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Animales , Quinasas p21 Activadas/metabolismo , Quinasas p21 Activadas/genética , Masculino , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ratones , Apoptosis/efectos de los fármacos , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Adulto , Adolescente , Estabilidad Proteica/efectos de los fármacos , Ratones Desnudos , Adulto Joven , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Invasividad Neoplásica

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AIM: To evaluate the efficacy and safety of dapagliflozin versus placebo as an add-on in patients with type 2 diabetes who did not achieve adequate glycaemic control with evogliptin and metformin combination. PATIENTS AND METHODS: In this multicentre, randomized, double-blind, placebo-controlled Phase 3 trial, patients with glycated haemoglobin (HbA1c) levels ≥7.0% (≥53 mmol/mol) and ≤10.5% (≤91 mmol/mol) who had received stable-dose metformin (≥1000 mg) and evogliptin (5 mg) for at least 8 weeks were randomized to receive dapagliflozin 10 mg or placebo once daily for 24 weeks. Participants continued treatment with metformin and evogliptin. The primary endpoint was change in HbA1c level after 24 weeks of treatment from baseline level. RESULTS: In total, 198 patients were randomized, and 195 patients were included in the efficacy analyses (dapagliflozin: 96, placebo: 99). At Week 24, dapagliflozin significantly reduced HbA1c levels. The least squares mean difference in HbA1c level change from baseline after 24 weeks of treatment was -0.70% (-7.7 mmol/mol) (p < 0.0001). The proportion of participants achieving HbA1c <7.0% (≥53 mmol/mol) was higher in the dapagliflozin group than in the placebo group. Compared to placebo, dapagliflozin significantly reduced fasting plasma glucose, mean daily glucose, 2-h postprandial plasma glucose, fasting insulin, uric acid and gamma-glutamyl transferase levels, homeostatic model assessment for insulin resistance index, body weight, hepatic steatosis index, and albuminuria. Adiponectin level significantly increased from baseline level after 24 weeks of dapagliflozin treatment. Adverse event rates were similar in the two groups. CONCLUSION: Dapagliflozin add-on to evogliptin plus metformin improved glycaemic control and was well tolerated by the target patients.

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BRCA genes have well-known associations with breast and ovarian cancers. However, variations in the BRCA gene, especially germline variations, have also been reported in colorectal cancer (CRC). We present the case of a rectal cancer with a germline BRCA1 variation inherited from the paternal side. A 39-year-old male was admitted with rectal cancer. The patient underwent surgical resection and the pathologic diagnosis was adenocarcinoma. Next-generation sequencing was performed and a BRCA1 variant was detected. Reviewing the public database and considering the young age of the patient, the variant was suggested to be germline. The patient's father had had prostate cancer and next-generation sequencing testing revealed an identical BRCA1 variant. In the BRCA cancer group, there is relatively little attention paid to male cancers. The accumulation of male CRC cases linked to BRCA variations may help clarify the potential pathological relationship between the two.

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Colletotrichum species are notorious for causing anthracnose on many fruits, leading to significant economic losses worldwide. As a model, we functionally characterized cys2-his2 (C2H2) zinc finger proteins (CsCZFs) in Colletotrichum scovillei, a major causal agent of pepper fruit anthracnose in many countries. In all, 62 CsCZFs were identified by in silico genomic analysis. Twelve were selected based on their expression profiles to generate targeted deletion mutants for functional investigation. ΔCsczf1 markedly reduced conidiation and constitutive expression of CsCZF1 partially recovered conidiation in an asexual reproduction-defective mutant, ΔCshox2. Deletion of CsCZF12, orthologous to the calcineurin-responsive transcription factor Crz1, impaired autophagy in C. scovillei. ΔCsczf9 was defective in surface recognition, appressorium formation, and suppression of host defenses. CsCZF9 was identified as an essential and novel regulator under the control of the mitogen-activated protein kinase (CsPMK1) in an early step of appressorium development in C. scovillei. This study provides novel insights into CsCZF-mediated regulation of differentiation and pathogenicity in C. scovillei, contributing to understanding the regulatory mechanisms governing fruit anthracnose epidemics.IMPORTANCEThe phytopathogenic fungus Colletotrichum scovillei is known to cause serious anthracnose on chili pepper. However, the molecular mechanism underlying anthracnose caused by this fungus remains largely unknown. Here, we systematically analyzed the functional roles of cys2-his2 zinc finger proteins (CsCZFs) in the dissemination and pathogenic development of this fungus. Our results showed that CsCZF1 plays an important role in conidiation and constitutive expression of CsCZF1 restored conidiation in an asexual reproduction-defective mutant, ΔCshox2. The CsCZF9, a novel target of the mitogen-activated protein kinase (CsPMK1), is essential for surface recognition to allow appressorium formation and suppression of host defenses in C. scovillei. The CsCZF12, orthologous to the calcineurin-responsive transcription factor Crz1, is involved in the autophagy of C. scovillei. Our findings reveal a comprehensive mechanism underlying CsCZF-mediated regulation of differentiation and pathogenicity of C. scovillei, which contributes to the understanding of fruit anthracnose epidemics and the development of novel strategies for disease management.

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PURPOSE: To investigate the risk of visual impairment (VI) based on the presence or absence of four diseases: hypertension (HTN), diabetes mellitus (DM), glaucoma, and diabetic retinopathy (DR). METHODS: This retrospective population-based study included 1,000,000 randomly selected participants from the National Health Checkup Program database between 2015 and 2016. VI was defined as a presenting visual acuity ≤ 0.5 in the better eye. The participants were divided into 12 groups according to the presence or absence of disease. Adjusting for age and sex, the risk of VI in each disease group was analyzed and compared with the others. RESULTS: Among the 1,000,000 participants, 88,931 (8.89%) had VI. The odds ratios (ORs) of age, male sex, HTN, DM, glaucoma, and DR for VI were 1.06 (95% CI, 1.05-1.06), 0.52 (95% CI, 0.52-0.53), 1.11 (95% CI, 1.09-1.13), 1.07 (95% CI, 1.05-1.09), 0.92 (95% CI, 0.90-0.74), and 1.29 (95% CI, 1.25-1.34), respectively (all P < 0.001). The group with HTN, DM, glaucoma, and DR had the highest OR of 1.98 (P < 0.001) compared to the healthy group. HTN, DM, and DR were positively correlated with VI in all groups. Glaucoma was positively correlated in the group with DM and DR and in the group with HTN, DM, and DR (ORs 1.18, 1.11, all P < 0.05); however, it demonstrated a negative correlation in the other groups (ORs 0.85-0.93, all P < 0.05). CONCLUSION: HTN, DM, and DR, either alone or in combination, increase the risk of VI. Glaucoma also increases the risk when combined with DR; however, it has a negative correlation with VI in the absence of DR. Periodic ophthalmologic examinations for glaucoma, which primarily affects the peripheral visual field and not central visual acuity, might help prevent VI caused by other diseases.

Asunto(s)

Comorbilidad , Retinopatía Diabética , Glaucoma , Hipertensión , Trastornos de la Visión , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Glaucoma/epidemiología , Glaucoma/complicaciones , Retinopatía Diabética/epidemiología , Trastornos de la Visión/epidemiología , Hipertensión/epidemiología , Hipertensión/complicaciones , Factores de Riesgo , Anciano , Adulto , Diabetes Mellitus/epidemiología , Agudeza Visual

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Magnetoresistance is a fundamental transport phenomenon that is essential for reading the magnetic states for various information storage, innovative computing and sensor devices. Recent studies have expanded the scope of magnetoresistances to the nonlinear regime, such as a bilinear magnetoelectric resistance (BMER), which is proportional to both electric field and magnetic field. Here we demonstrate that the BMER is a general phenomenon that arises even in three-dimensional systems without explicit momentum-space spin textures. Our theory suggests that the spin Hall effect enables the BMER provided that the magnitudes of spin accumulation at the top and bottom interfaces are not identical. The sign of the BMER follows the sign of the spin Hall effect of heavy metals, thereby evidencing that the BMER originates from the bulk spin Hall effect. Our observation suggests that the BMER serves as a general nonlinear transport characteristic in three-dimensional systems, especially playing a crucial role in antiferromagnetic spintronics.

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This study was performed to evaluate the effects of rye silage treated with sodium formate (Na-Fa) and lactic acid bacteria (LAB) inoculants on the ruminal fermentation characteristics, methane yield and energy balance in Hanwoo steers. Forage rye was harvested in May 2019 and ensiled without additives (control) or with either a LAB inoculant or Na-Fa. The LAB (Lactobacillus plantarum) were inoculated at 1.5 × 1010 CFU/g fresh matter, and the inoculant was sprayed onto the forage rye during wrapping at a rate of 4 L/ton of fresh rye forage. Sixteen percent of the Na-Fa solution was sprayed at a rate of approximately 6.6 L/ton. Hanwoo steers (body weight 275 ± 8.4 kg (n = 3, group 1); average body weight 360 ± 32.1 kg (n = 3, group 2)) were allocated into two pens equipped with individual feeding gates and used in duplicated 3 × 3 Latin square design. The experimental diet was fed twice daily (09:00 and 18:00) during the experimental period. Each period comprised 10 days for adaptation to the pen and 9 days for measurements in a direct respiratory chamber. The body weights of the steers were measured at the beginning and at the end of the experiment. Feces and urine were collected for 5 days after 1 day of adaptation to the chamber, methane production was measured for 2 days, and ruminal fluid was collected on the final day. In the LAB group, the ratio of acetic acid in the rumen fluid was significantly lower (p = 0.044) and the ratio of propionic acid in the rumen fluid was significantly higher (p = 0.017). Methane production per DDMI of the Na-FA treatment group was lower than that of the other groups (p = 0.052), and methane production per DNDFI of the LAB treatment group was higher than that of the other groups (p = 0.056). The use of an acid-based additive in silage production has a positive effect on net energy and has the potential to reduce enteric methane emissions in ruminants.

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Metabolismo Energético , Fermentación , Formiatos , Metano , Rumen , Secale , Ensilaje , Animales , Bovinos , Metano/biosíntesis , Metano/metabolismo , Ensilaje/análisis , Ensilaje/microbiología , Formiatos/farmacología , Formiatos/metabolismo , Rumen/microbiología , Rumen/metabolismo , Masculino , Fermentación/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Metabolismo Energético/fisiología , Lactobacillus plantarum/metabolismo , Alimentación Animal/análisis

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We report a systematic Raman spectroscopy investigation of chemical vapor deposited 2D nonlayered Cr2S3, with both linearly and circularly polarized light over a wide temperature range (5-300 K). Temperature-dependent Raman spectra exhibit a good linear relationship between the peak positions of the phonon modes and temperature. Angle-resolved polarized Raman spectra reveal the polarization-dependent optical response of in-plane and out-of-plane phonon modes. Helicity-dependent Raman investigations complete definite assignment of all the phonon modes observed in the Raman spectra of 2D nonlayered Cr2S3 by the optical selection rule based on a Raman tensor. Our work realizes clear phonon mode identification over a wide temperature range for the emerging material 2D Cr2S3, an important representative of nonlayered 2D system with unique properties for optoelectronic and spintronic applications.

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Stem cell-based therapies offer promising avenues for treating inflammatory diseases owing to their immunomodulatory properties. However, challenges persist regarding their survival and efficacy in inflamed tissues. Our study introduces a novel approach by engineering adipose-derived stem cells (ADSCs) to enhance their viability in inflammatory environments and boost the secretion of paracrine factors for treating inflammatory bowel disease (IBD). An arginine-glycine-aspartate peptide-poly (ethylene glycol)-chlorin e6 conjugate (RPC) was synthesized and coupled with ADSCs, resulting in RPC-labeled ADSCs (ARPC). This conjugation strategy employed RGD-integrin interaction to shield stem cells and allowed visualization and tracking using chlorin e6. The engineered ARPC demonstrated enhanced viability and secretion of paracrine factors upon light irradiation, regulating the inflammatory microenvironment. RNA-sequencing analysis unveiled pathways favoring angiogenesis, DNA repair, and exosome secretion in ARPC(+) while downregulating inflammatory pathways. In in vivo models of acute and chronic IBD, ARPC(+) treatment led to reduced inflammation, preserved colon structure, and increased populations of regulatory T cells, highlighting its therapeutic potential. ARPC(+) selectively homed to inflammatory sites, demonstrating its targeted effect. Overall, ARPC(+) exhibits promise as an effective and safe therapeutic strategy for managing inflammatory diseases like IBD by modulating immune responses and creating an anti-inflammatory microenvironment.

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Objective: The objective of this study was to determine the implementation, clinical barriers, and unmet needs of repetitive transcranial magnetic stimulation (rTMS) and neuro-navigation systems for stroke rehabilitation. Design: We employed a nationwide survey via Google Forms (web and mobile) consisting of 36 questions across rTMS and neuro-navigation systems, focusing on their implementation, perceptions, and unmet needs in stroke recovery. The survey targeted physiatrists registered in the Korean Society for Neuro-rehabilitation and in rehabilitation hospitals in South Korea. Results: Of 1,129 surveys distributed, 122 responses were analyzed. Most respondents acknowledged the effectiveness of rTMS in treating post-stroke impairments; however, they highlighted significant unmet needs in standardized treatment protocols, guidelines, education, device usability, and insurance coverage. Unmet needs for neuro-navigation were also identified; only 7.4% of respondents currently used such systems, despite acknowledging their potential to enhance treatment accuracy. Seventy percent of respondents identified lack of prescription coverage, time and errors in preparation, and device cost as barriers to clinical adoption of neuro-navigation systems. Conclusion: Despite recognition of the potential of rTMS in stroke rehabilitation, there is a considerable gap between research evidence and clinical practice. Addressing these challenges, establishing standardized protocols, and advancing accessible neuro-navigation systems could significantly enhance the clinical application of rTMS, offering a more personalized, effective treatment modality for stroke recovery.

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BACKGROUND: The Kirsten rat sarcoma virus (KRAS) is a prominent proto-oncogene. Several treatments for KRAS mutations have been developed. However, KRAS amplification, a KRAS alteration, is poorly understood, and there is currently no appropriate treatment other than conventional chemotherapy. This study aimed to elucidate the role of KRAS amplification in different types of cancers. METHODS: From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3895 patients with 37 different cancer types at the Samsung Medical Center. We analyzed the distribution of KRAS amplification according to cancer type and its correlation with tumor mutation burden (TMB). Concomitant KRAS mutations were also identified. RESULTS: Of the total 3895 patients, 99 (2.5 %) had KRAS amplification. The highest frequency of KRAS amplification was detected in 2 % (27/1350) of patients with colorectal cancer, followed by 3.48 % (32/920) of patients with gastric cancer and 3.88 % (9/232) patients with of pancreatic cancer. MSI-High was not detected in patients with KRAS amplification. There was no correlation between KRAS copy number variation and TMB status. Among patients with KRAS amplification, 27.3 % (27/99) had a concomitant KRAS mutation. More than 50 % of patients had G12D or G12V mutations. In gastric cancer, patients with both KRAS amplification and mutation were extremely rare at 3.1 % (1/32); however, in colorectal cancer, more than half of the patients had KRAS amplification and mutation (51.9 %, 14/27). KRAS amplification and mutations are associated with mutations in tumor suppressor genes TP53, BRCA2, ARID1B, and PTCH1. CONCLUSIONS: Of the 3895 patients with metastatic solid tumors, 99 (2.5 %) had KRAS amplification, and next-generation sequencing analysis provided a deeper understanding of KRAS amplification.

Asunto(s)

Amplificación de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Proteínas Proto-Oncogénicas p21(ras)/genética , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neoplasias/genética , Neoplasias/patología , Adulto , Prevalencia , Biomarcadores de Tumor/genética , Metástasis de la Neoplasia/genética

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The systemic delivery of oligonucleotide therapeutics to the brain is challenging but highly desirable for the treatment of brain diseases undruggable with traditional small-molecule drugs. In this study, a set of DNA nanostructures is prepared and screened them to develop a protein corona-assisted platform for the brain delivery of oligonucleotide therapeutics. The biodistribution analysis of intravenously injected DNA nanostructures reveals that a cube-shaped DNA nanostructure (D-Cb) can penetrate the brain-blood barrier (BBB) and reach the brain tissue. The brain distribution level of D-Cb is comparable to that of other previous nanoparticles conjugated with brain-targeting ligands. Proteomic analysis of the protein corona formed on D-Cb suggests that its brain distribution is driven by endothelial receptor-targeting ligands in the protein corona, which mediate transcytosis for crossing the BBB. D-Cb is subsequently used to deliver an antisense oligonucleotide (ASO) to treat glioblastoma multiforme (GBM) in mice. While free ASO is unable to reach the brain, ASO loaded onto D-Cb is delivered efficiently to the brain tumor region, where it downregulates the target gene and exerts an anti-tumor effect on GBM. D-Cb is expected to serve as a viable platform based on protein corona formation for systemic brain delivery of oligonucleotide therapeutics.

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Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

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Background and Objective: Early discharge following robot-assisted kidney transplantation (RAKT) is a cost-effective strategy for reducing healthcare expenses while maintaining favorable short- and long-term prognoses. This study aims to identify predictors of postoperative delayed discharge in RAKT patients and develop a predictive model to enhance clinical outcomes. Materials and Methods: This retrospective study included 146 patients aged 18 years and older who underwent RAKT at a single tertiary medical center from August 2020 to January 2024. Data were collected on demographics, comorbidities, social and medical histories, preoperative labs, surgical information, intraoperative data, and postoperative outcomes. The primary outcome was delayed postoperative discharge (length of hospital stay > 7 days). Risk factors for delayed discharge were identified through univariate and multivariate regression analyses, leading to the development of a risk scoring system, the effectiveness of which was evaluated through receiver operating characteristic curve analysis. Results: 110 patients (74.8%) were discharged within 7 days post-transplant, while 36 (24.7%) remained hospitalized for 8 days or longer. Univariate and multivariate logistic regression analyses identified ABO incompatibility, BUN levels, anesthesia time, and vasodilator use as risk factors for delayed discharge. The RAKT score, incorporating these factors, demonstrated a predictive performance with a C-statistic of 0.789. Conclusions: This study identified risk factors for delayed discharge after RAKT and developed a promising risk scoring system for real-world clinical application, potentially improving postoperative outcome stratification in RAKT recipients.

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Trasplante de Riñón , Tiempo de Internación , Procedimientos Quirúrgicos Robotizados , Humanos , Femenino , Masculino , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Persona de Mediana Edad , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Factores de Riesgo , Tiempo de Internación/estadística & datos numéricos , Adulto , Curva ROC , Complicaciones Posoperatorias/epidemiología , Anciano

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PURPOSE: Endurance exercise induces muscle fiber-type shifting and autophagy; however, the potential role of autophagy in muscle fiber-type transformation remains unclear. This study examined the relationship between muscle fiber-type shifting and autophagy in the soleus (SOL) and extensor digitorum longus (EDL) muscles, which are metabolically discrete muscles. METHODS: Male C57BL/6J mice were randomly assigned to sedentary control (CON) and exercise (EXE) groups. After 1 week of acclimation to treadmill running, the mice in the EXE group ran at 12-15 m/min, 60 min/day, 5 days/week for 6 weeks. All mice were sacrificed 90 min after the last exercise session, and the targeted tissues were rapidly dissected. The right side of the tissues was used for western blot analysis, whereas the left side was subjected to immunohistochemical analysis. RESULTS: Endurance exercise resulted in muscle fiber-type shifting (from type IIa to type I) and autophagy (an increase in LC3-II) in the SOL muscle. However, muscle fiber-type transformation and autophagy were not correlated in the SOL and EDL muscles. Interestingly, in contrast to the canonical autophagy signaling pathways, our study showed that exercise-induced autophagy concurs with enhanced anabolic (increased p-AKTSer473/AKT and p-mTOR/mTORSer2448 ratios) and suppressed catabolic (reduced p-AMPKThr172/AMPK ratio) states. CONCLUSION: Our findings demonstrate that chronic endurance exercise-induced muscle fiber-type transformation and autophagy occur in a muscle-specific manner (e.g., SOL). More importantly, our study suggests that endurance training-induced SOL muscle fiber-type transition may underlie metabolic modulations caused by the AMPK and AKT/mTOR signaling pathways rather than autophagy.

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The cardiac conduction system (CCS) is a network of specialized cardiomyocytes that coordinates electrical impulse generation and propagation for synchronized heart contractions. Although the components of the CCS, including the sinoatrial node, atrioventricular node, His bundle, bundle branches, and Purkinje fibers, were anatomically discovered more than 100 years ago, their molecular constituents and regulatory mechanisms remain incompletely understood. Here, we demonstrate the transcriptomic landscape of the postnatal mouse CCS at a single-cell resolution with spatial information. Integration of single-cell and spatial transcriptomics uncover region-specific markers and zonation patterns of expression. Network inference shows heterogeneous gene regulatory networks across the CCS. Notably, region-specific gene regulation is recapitulated in vitro using neonatal mouse atrial and ventricular myocytes overexpressing CCS-specific transcription factors, Tbx3 and/or Irx3. This finding is supported by ATAC-seq of different CCS regions, Tbx3 ChIP-seq, and Irx motifs. Overall, this study provides comprehensive molecular profiles of the postnatal CCS and elucidates gene regulatory mechanisms contributing to its heterogeneity.

Asunto(s)

Sistema de Conducción Cardíaco , Proteínas de Homeodominio , Miocitos Cardíacos , Proteínas de Dominio T Box , Animales , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Ratones , Miocitos Cardíacos/metabolismo , Sistema de Conducción Cardíaco/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Redes Reguladoras de Genes , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Regulación de la Expresión Génica , Animales Recién Nacidos , Análisis de la Célula Individual , Transcriptoma , Ramos Subendocárdicos/metabolismo , Ramos Subendocárdicos/fisiología , Nodo Atrioventricular/metabolismo , Nodo Sinoatrial/metabolismo , Fascículo Atrioventricular/metabolismo

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Células Madre Pluripotentes Inducidas , Miocitos Cardíacos , Sitios de Carácter Cuantitativo , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Miocitos Cardíacos/metabolismo , Variación Genética

RESUMEN

BACKGROUND: Gait analysis is essential for evaluating locomotor function and fall risk, particularly in the elderly and in various musculoskeletal disorders. Traditional gait analysis systems face challenges such as technical difficulties, high cost, and complexity of use. Therefore, there is a need for a more accessible and cost-effective system with a wider clinical applicability. RESEARCH QUESTION: This study aimed to validate the newly developed IB-gait® system (InBody, Republic of Korea), a camera-based gait analysis tool, by comparing it against the VICON system. METHODS: A total of 28 community-dwelling adults without gait abnormalities (mean age 24.9 years) were enrolled in this study. The participants underwent gait analysis at their self-selected speed using VICON and IB-gait® simultaneously. Nine spatiotemporal gait parameters, including stride length (m), step length (m), stride duration (s), double-limb duration (s), stance phase (s), swing phase (s), cadence (velocity × 120/stride length), and gait velocity (m/s) were measured. The agreement between the two systems was tested using Bland-Altman plots and intraclass correlation coefficients (ICC). RESULTS: The IB-gait® showed a high degree of agreement with the VICON system in most gait parameters. The ICC showed excellent reliability for stride length (0.97), step length (0.92), gait velocity (0.97), cadence (0.97), and stride duration (0.79). However, it showed lower reliability in time-based parameters, including double-limb duration (0.12), stance phase (0.54), swing phase (0.241), and stance/swing phase ratio (0.11). SIGNIFICANCE: The IB-gait® system appears to be a feasible and cost-effective alternative to VICON system for gait analysis, particularly showing a high level of agreement in the distance-based parameters. Its practicality in clinical settings makes it a valuable tool for widespread use in gait analysis. However, further refinement of time-based parameter measurements and validation in diverse patient populations are needed to enhance its applicability.