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1.
Exp Mol Med ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866910

RESUMO

Neoantigens are ideal targets for cancer immunotherapy because they are expressed de novo in tumor tissue but not in healthy tissue and are therefore recognized as foreign by the immune system. Advances in next-generation sequencing and bioinformatics technologies have enabled the quick identification and prediction of tumor-specific neoantigens; however, only a small fraction of predicted neoantigens are immunogenic. To improve the predictability of immunogenic neoantigens, we developed the in silico neoantigen prediction workflows VACINUSpMHC and VACINUSTCR: VACINUSpMHC incorporates physical binding between peptides and MHCs (pMHCs), and VACINUSTCR integrates T cell reactivity to the pMHC complex through deep learning-based pairing with T cell receptors (TCRs) of putative tumor-reactive CD8 tumor-infiltrating lymphocytes (TILs). We then validated our neoantigen prediction workflows both in vitro and in vivo in patients with hepatocellular carcinoma (HCC) and in a B16F10 mouse melanoma model. The predictive abilities of VACINUSpMHC and VACINUSTCR were confirmed in a validation cohort of 8 patients with HCC. Of a total of 118 neoantigen candidates predicted by VACINUSpMHC, 48 peptides were ultimately selected using VACINUSTCR. In vitro validation revealed that among the 48 predicted neoantigen candidates, 13 peptides were immunogenic. Assessment of the antitumor efficacy of the candidate neoepitopes using a VACINUSTCR in vivo mouse model suggested that vaccination with the predicted neoepitopes induced neoantigen-specific T cell responses and enabled the trafficking of neoantigen-specific CD8 + T cell clones into the tumor tissue, leading to tumor suppression. This study showed that the prediction of immunogenic neoantigens can be improved by integrating a tumor-reactive TIL TCR-pMHC ternary complex.

2.
Parasites Hosts Dis ; 62(2): 243-250, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38835265

RESUMO

We investigated organ specific Toxocara canis larval migration in mice infected with T. canis larvae. We observed the worm burden and systemic immune responses. Three groups of BALB/c mice (n=5 each) were orally administered 1,000 T. canis 2nd stage larvae to induce larva migrans. Mice were sacrificed at 1, 3, and 5 weeks post-infection. Liver, lung, brain, and eye tissues were collected. Tissue from 2 mice per group was digested for larval count, while the remaining 3 mice underwent histological analysis. Blood hematology and serology were evaluated and compared to that in a control uninfected group (n=5) to assess the immune response. Cytokine levels in bronchoalveolar lavage (BAL) fluid were also analyzed. We found that, 1 week post-infection, the mean parasite load in the liver (72±7.1), brain (31±4.2), lungs (20±5.7), and eyes (2±0) peaked and stayed constant until the 3 weeks. By 5-week post-infection, the worm burden in the liver and lungs significantly decreased to 10±4.2 and 9±5.7, respectively, while they remained relatively stable in the brain and eyes (18±4.2 and 1±0, respectively). Interestingly, ocular larvae resided in all retinal layers, without notable inflammation in outer retina. Mice infected with T. canis exhibited elevated levels of neutrophils, monocytes, eosinophils, and immunoglobulin E. At 5 weeks post-infection, interleukin (IL)-5 and IL-13 levels were elevated in BAL fluid. Whereas IL-4, IL-10, IL-17, and interferon-γ levels in BAL fluid were similar to that in controls. Our findings demonstrate that a small portion of T. canis larvae migrate to the eyes and brain within the first week of infection. Minimal tissue inflammation was observed, probably due to increase of anti-inflammatory cytokines. This study contributes to our understanding of the histological and immunological responses to T. canis infection in mice, which may have implications to further understand human toxocariasis.


Assuntos
Encéfalo , Citocinas , Larva , Fígado , Pulmão , Camundongos Endogâmicos BALB C , Toxocara canis , Toxocaríase , Animais , Toxocara canis/imunologia , Toxocaríase/imunologia , Toxocaríase/patologia , Toxocaríase/parasitologia , Larva/imunologia , Camundongos , Citocinas/metabolismo , Pulmão/parasitologia , Pulmão/imunologia , Pulmão/patologia , Fígado/parasitologia , Fígado/patologia , Fígado/imunologia , Encéfalo/parasitologia , Encéfalo/imunologia , Encéfalo/patologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/parasitologia , Feminino , Carga Parasitária , Olho/parasitologia , Olho/imunologia , Olho/patologia , Modelos Animais de Doenças
3.
Int J Mol Sci ; 25(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38892385

RESUMO

Aging leads to tissue and cellular changes, often driven by oxidative stress and inflammation, which contribute to age-related diseases. Our research focuses on harnessing the potent anti-inflammatory and antioxidant properties of Korean Ulmus macrocarpa Hance, a traditional herbal remedy, to address muscle loss and atrophy. We evaluated the effects of Ulmus extract on various parameters in a muscle atrophy model, including weight, exercise performance, grip strength, body composition, muscle mass, and fiber characteristics. Additionally, we conducted Western blot and RT-PCR analyses to examine muscle protein regulation, apoptosis factors, inflammation, and antioxidants. In a dexamethasone-induced muscle atrophy model, Ulmus extract administration promoted genes related to muscle formation while reducing those associated with muscle atrophy. It also mitigated inflammation and boosted muscle antioxidants, indicating a potential improvement in muscle atrophy. These findings highlight the promise of Ulmus extract for developing pharmaceuticals and supplements to combat muscle loss and atrophy, paving the way for clinical applications.


Assuntos
Antioxidantes , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Extratos Vegetais , Sarcopenia , Ulmus , Animais , Sarcopenia/tratamento farmacológico , Sarcopenia/patologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Camundongos , Ulmus/química , Antioxidantes/farmacologia , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
5.
Sci Robot ; 9(90): eadk6903, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38809996

RESUMO

Avian eyes have deep central foveae as a result of extensive evolution. Deep foveae efficiently refract incident light, creating a magnified image of the target object and making it easier to track object motion. These features are essential for detecting and tracking remote objects in dynamic environments. Furthermore, avian eyes respond to a wide spectrum of light, including visible and ultraviolet light, allowing them to efficiently distinguish the target object from complex backgrounds. Despite notable advances in artificial vision systems that mimic animal vision, the exceptional object detection and targeting capabilities of avian eyes via foveated and multispectral imaging remain underexplored. Here, we present an artificial vision system that capitalizes on these aspects of avian vision. We introduce an artificial fovea and vertically stacked perovskite photodetector arrays whose designs were optimized by theoretical simulations for the demonstration of foveated and multispectral imaging. The artificial vision system successfully identifies colored and mixed-color objects and detects remote objects through foveated imaging. The potential for use in uncrewed aerial vehicles that need to detect, track, and recognize distant targets in dynamic environments is also discussed. Our avian eye-inspired perovskite artificial vision system marks a notable advance in bioinspired artificial visions.


Assuntos
Biomimética , Aves , Compostos de Cálcio , Óxidos , Titânio , Visão Ocular , Animais , Aves/fisiologia , Visão Ocular/fisiologia , Biomimética/instrumentação , Fóvea Central/fisiologia , Desenho de Equipamento , Materiais Biomiméticos , Simulação por Computador
6.
Circulation ; 149(24): 1865-1874, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38690659

RESUMO

BACKGROUND: The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction. METHODS: The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS: The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12). CONCLUSIONS: Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Insuficiência Cardíaca , Insuficiência da Valva Mitral , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Insuficiência da Valva Mitral/tratamento farmacológico , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Masculino , Feminino , Idoso , Método Duplo-Cego , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Resultado do Tratamento , Fragmentos de Peptídeos/sangue , Função Ventricular Esquerda/efeitos dos fármacos , Peptídeo Natriurético Encefálico
7.
Int Arch Occup Environ Health ; 97(5): 537-543, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38564018

RESUMO

PURPOSE: This study aimed to reveal the relationship of the days of experiencing sickness presentism and depressive symptoms among Korean workers. Sickness presenteeism which defined as the act of going to work despite being feeling unhealthy triggers various adverse effects on mental health, including increased risks of depression. Furthermore, Sickness presenteeism is a major social issue causing substantial socioeconomic costs. METHODS: The data of 25120 participants from sixth Korean Working Condition Survey was utilized in this cross-sectional study. Sickness presenteeism was defined using a self-reported questionnaire and depressive symptoms were assessed by WHO well-being index. Multivariate logistic regression analysis was conducted to calculate the odd ratios for depressive symptoms regarding the number of days experiencing sickness presenteeism. We calculated odds ratios (ORs) and 95% confidence interval (95% CI) for depressive symptoms after categorizing participants into three groups based on the duration of experiencing sickness presenteeism, using cut-off values of 3 and 5 days. RESULTS: Workers who have experienced sickness presenteeism for more than 5 days were at highest risk for depressive symptoms than referent group (OR 2.87; 95% CI 2.17-3.76 in male, OR 3.86; 95% CI 3.02-4.91 in female). Furthermore, there was a trend of increasing risk for depressive symptom as the duration of experiencing sickness presenteeism extended. CONCLUSION: This study presents the association between experiencing sickness presenteeism in the previous 12 months and depressive symptoms. Based on the results, we provide individual and organizational strategies of reducing sickness presenteeism. Also, screening for workers who have experienced sickness presenteeism are needed to ensure good mental health.


Assuntos
Depressão , Presenteísmo , Humanos , Masculino , Feminino , Presenteísmo/estatística & dados numéricos , Estudos Transversais , Depressão/epidemiologia , Adulto , República da Coreia/epidemiologia , Pessoa de Meia-Idade , Inquéritos e Questionários , Licença Médica/estatística & dados numéricos , Adulto Jovem , Fatores de Risco , Condições de Trabalho
8.
Bioengineering (Basel) ; 11(4)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38671801

RESUMO

XRD diffraction and IR absorption were investigated for raw loess powder and heat-treated loess powder. Raw loess retains its useful minerals, but loses their beneficial properties when calcined at 850 °C and 1050 °C. To utilize the useful minerals, loess balls were made using a low-temperature wet-drying method. The radiant energy and transmittance were measured for the loess balls. Far-infrared ray (FIR) emitted from loess bio-balls is selectively absorbed as higher vibrational energy by water molecules. FIR can raise the body's core temperature, thereby improving blood flow through the body's thermoregulatory mechanism. In an exploratory study with 40 participants, when the set temperature of the loess ball mat was increased from 25 °C to 50 °C, blood flow increased by 39.01%, from 37.48 mL/min to 52.11 mL/min, in the left middle finger; in addition, it increased by 39.62%, from 37.15 mL/min to 51.87 mL/min, in the right middle finger. The FIR emitted from loess balls can be widely applied, in various forms, to diseases related to blood flow, such as cold hands and feet, diabetic foot, muscle pain, and menstrual pain.

9.
Cancers (Basel) ; 16(8)2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38672574

RESUMO

Hepatocellular carcinoma (HCC) is a highly aggressive form of liver cancer with poor prognosis. The lack of reliable biomarkers for early detection and accurate diagnosis and prognosis poses a significant challenge to its effective clinical management. In this study, we investigated the diagnostic and prognostic potential of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in peripheral blood mononuclear cells (PBMCs) in HCC. PD-1 and CTLA-4 gene expression was analyzed comparatively using PBMCs collected from HCC patients and healthy individuals. The results revealed higher PD-1 gene expression levels in patients with multifocal tumors, lymphatic invasion, or distant metastasis than those in their control counterparts. However, conventional serum biomarkers of liver function do not exhibit similar correlations. In conclusion, PD-1 gene expression is associated with OS and PFS and CTLA-4 gene expression is associated with OS, whereas the serum biomarkers analyzed in this study show no significant correlation with survival in HCC. Hence, PD-1 and CTLA-4 expressed in PBMCs are considered potential prognostic biomarkers for patients with HCC that can facilitate prediction of malignancy, response to currently available HCC treatments, and overall survival.

10.
J Dent Sci ; 19(2): 804-812, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38618071

RESUMO

Background/purpose: The combination of recombinant human bone morphogenetic protein-2 (rhBMP-2) with a carrier material has not been extensively studied. This study aimed to evaluate the clinical, radiological, and histomorphometric outcomes of sinus floor augmentation using a 3:7 mixture of cancellous and cortical freeze-dried bone allografts (mixed AG) combined with rhBMP-2. Materials and methods: Mixed AG was used for sinus floor augmentation in a total of 21 patients with a residual alveolar bone height <5 mm. Among the total 47 sites, augmentation with and without rhBMP-2 was performed in 26 and 21 sites, respectively. Radiographic parameters were assessed using cone-beam computed tomography. After a six-month healing period, core biopsies were harvested for histomorphometric analysis. Results: The bone gain after healing was 13.36 ± 3.9 mm and 12.07 ± 3.8 mm in the mixed AG alone and mixed AG with rhBMP-2 groups, respectively. The survival rate of implants in both groups was 100% during the follow-up period. The proportion of newly formed bone was 24.6 ± 10.2% and 39.7 ± 18.3% in the mixed AG alone and mixed AG with rhBMP-2 groups, respectively (P < 0.05). Moreover, the percentage of residual graft material was 21.0 ± 12.2% and 9.6 ± 10.0% in the mixed AG alone and mixed AG with rhBMP-2 groups, respectively (P < 0.05). Conclusion: Mixed AG combined with rhBMP-2 could be a suitable material for sinus floor augmentation. This combination may reduce the treatment time and improve the predictability of implant placement.

11.
Gastric Cancer ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647977

RESUMO

BACKGROUND: During sentinel node navigation surgery in patients with gastric cancer, intraoperative pathologic examination of sentinel nodes is crucial in determining the extent of surgery. In this study, we evaluated the feasibility and accuracy of intraoperative pathologic protocols using data from a prospective, multicenter, randomized trial. METHODS: A retrospective analysis was conducted using data from the SEntinel Node ORIented Tailored Approach trials from 2013 to 2016. All sentinel lymph nodes were evaluated during surgery with hematoxylin-eosin (HE) staining using a representative section at the largest plane for lymph nodes. For permanent histologic evaluation, sentinel basin nodes were stained with HE and cytokeratin immunohistochemistry in formalin-fixed, paraffin-embedded (FFPE) sections and examined with HE for three deeper-step sections at 200-µm intervals. The failure rate of identification by frozen section and the metastasis rate in non-sentinel basins were investigated. RESULTS: Of the 237 patients who underwent sentinel node basin dissection, 30 had lymph node metastases on permanent pathology. Thirteen patients had macrometastasis confirmed in frozen sections as well as FFPE sections (failure rate: 0%). Patients with negative sentinel nodes in frozen sections but micrometastasis in FFPE sections had no lymph node recurrence during the follow-up period (0%, 0/6). However, in cases with tumor-positive nodes in frozen sections, metastases in non-sentinel basins were detected in the paraffin blocks (8.3%, 2/24). CONCLUSIONS: The single-section HE staining method is sufficient for detecting macrometastasis via intraoperative pathological examination. If a negative frozen-section result is confirmed, sentinel basin dissection can be performed safely. Otherwise, standard surgery is required.

14.
Sci Rep ; 14(1): 5249, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438557

RESUMO

To compare the efficacy of scleral buckling with adjuvant pneumatic retinopexy (SB with PR) and scleral buckling (SB) alone for primary rhegmatogenous retinal detachment (RRD). This retrospective and comparative study included patients who underwent SB with PR (n = 88) or SB alone (n = 161) for primary RRD. The primary anatomical success rate for SB with PR was 81.8%, whereas that for SB alone was 80.7% (P = 0.836). Among patients who achieved primary anatomical success, those in the SB with PR group showed postoperative epiretinal membrane (ERM) formation more frequently than those in the SB alone group (11 of 72 [15.3%] vs. 6 of 130 [4.6%]) (P = 0.009). The mean time to subretinal fluid absorption was not significantly different between the SB with PR and SB alone groups (11.2 ± 6.2 vs. 11.4 ± 5.8 months, P = 0.881). In the SB with PR group, retinal detachment involving ≥ three quadrants was a significant risk factor for surgical failure (hazard ratio, 3.04; P = 0.041). Adjuvant pneumatic retinopexy does not provide additional benefit in improving the surgical outcomes of SB for primary RRD repair.


Assuntos
Descolamento Retiniano , Recurvamento da Esclera , Humanos , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Adjuvantes Imunológicos , Adjuvantes Farmacêuticos
15.
Nurs Open ; 11(3): e2102, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38530867

RESUMO

AIMS: To evaluate the validity and reliability of the self-care behaviour scale for patients with left ventricular assist devices. DESIGN: Methodological study. METHODS: The English version of the scale was translated into Korean, and it was then back-translated into English. Survey data were collected from 32 patients with left ventricular assist device in South Korea, and construct validity, content validity and reliability were analysed. RESULTS: The original self-care behaviour scale comprises three domains and 33 items, whereas the Korean self-care behaviour scale comprises 27 items and five domains: device management, wound management, symptom monitoring, activated healthcare system and self-care management. Cronbach's alpha for the overall scale was 0.94, and that for the five domains ranged from 0.36 to 0.90. The intraclass correlation coefficient for the overall scale was 0.89, and the five domains ranged from 0.71 to 0.88. CONCLUSION: The newly evaluated scale would be valid and reliable in measure self-care behaviour for patients with a left ventricular assist device. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Patients can manage the left ventricular assist device on their own based on evidence and use it as a tool for effective communication with medical professionals.


Assuntos
Coração Auxiliar , Humanos , Autocuidado , Reprodutibilidade dos Testes , Inquéritos e Questionários , República da Coreia
16.
J Epidemiol ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38462531

RESUMO

Background Previous studies have suggested that employment insecurity is associated with adverse health outcomes. We explored the association between temporary employment and smoking behaviors.Methods We analyzed 11,795 workers (51,867 observations) from the Korea Health Panel Study (2009-2018). Employment types were categorized as regular, fixed-term, or daily, based on the duration of labor contract. The outcomes were current smoking status and changes in smoking behavior (initiation or cessation) in the following year. Generalized estimating equations were used to estimate odds ratio (OR) and 95% confidence interval (CI).Results The proportions of fixed-term and daily workers were 41.2% and 16.4% for women and 23.6% and 12.4% for men, respectively. Temporary employment was associated with increased odds of current smoking, while also demonstrating prospective associations with changes in smoking behaviors. For instance, in prospective analyses, male workers with fixed-term and daily employments were associated with a decreased likelihood of smoking cessation (OR:0.77; 95% CI:0.65-0.91 for fixed-term employment and OR:0.66; 95% CI:0.52-0.83 for daily employment) in the following year compared to those with regular employment. Moreover, those experiencing consecutive temporary employment was most inversely associated with smoking cessation in both men (OR:0.56; 95% CI:0.44-0.71) and women (OR:0.37; 95% CI:0.16-0.85) compared to those experiencing consecutive regular employment. However, no clear association between temporary employment and smoking initiation was observed in both men and women.Conclusions Temporary employment is directly associated with current smoking and inversely associated with smoking cessation. Policies are needed to improve job insecurity among temporary employees.

17.
J Chest Surg ; 57(2): 184-194, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38360679

RESUMO

Background: Left ventricular assist devices (LVADs) are widely employed as a therapeutic option for end-stage heart failure. We evaluated the outcomes associated with centrifugal-flow LVAD implantation, comparing 2 device models: the Heartmate 3 (HM3) and the Heartware Ventricular Assist Device (HVAD). Methods: Data were collected from patients who underwent LVAD implantation between June 1, 2015 and December 31, 2022. We analyzed overall survival, first rehospitalization, and early, late, and LVAD-related complications. Results: In total, 74 patients underwent LVAD implantation, with 42 receiving the HM3 and 32 the HVAD. A mild Interagency Registry for Mechanically Assisted Circulatory Support score was more common among HM3 than HVAD recipients (p=0.006), and patients receiving the HM3 exhibited lower rates of preoperative ventilator use (p=0.010) and extracorporeal membrane oxygenation (p=0.039). The overall early mortality rate was 5.4% (4 of 74 patients), with no significant difference between groups. Regarding early right ventricular (RV) failure, HM3 implantation was associated with a lower rate (13 of 42 [31.0%]) than HVAD implantation (18 of 32 [56.2%], p=0.051). The median rehospitalization-free period was longer for HM3 recipients (16.9 months) than HVAD recipients (5.3 months, p=0.013). Furthermore, HM3 recipients displayed a lower incidence of late hemorrhagic stroke (p=0.016). In the multivariable analysis, preoperative use of continuous renal replacement therapy (odds ratio, 22.31; p=0.002) was the only significant predictor of postoperative RV failure. Conclusion: The LVAD models (HM3 and HVAD) demonstrated comparable overall survival rates. However, the HM3 was associated with a lower risk of late hemorrhagic stroke.

18.
Am J Cardiovasc Drugs ; 24(2): 313-324, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38413500

RESUMO

BACKGROUND: The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy. METHODS: Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care. RESULTS: Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤ 40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF > 40%). CONCLUSIONS: Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum.


Assuntos
Compostos Benzidrílicos , Glucosídeos , Insuficiência Cardíaca , Humanos , Análise Custo-Benefício , Volume Sistólico , República da Coreia
19.
J Mol Histol ; 55(2): 149-157, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38407765

RESUMO

Cytodifferentiation of odontogenic cells, a late stage event in odontogenesis is based on gene regulation. However, studies on the identification of the involved genes are scarce. The present study aimed to search for molecules for the cytodifferentiation of ameloblastic cells in rats. Differential display-PCR revealed a differentially expressed gene between cap/early bell stage and hard tissue formation stage in molars. This gene was identified as N-myc Downregulated Gene 1 (Ndrg1), which is the first report in tooth development. Real time PCR and western blotting confirmed that the mRNA level of Ndrg1 was higher during enamel formation than the cap stage. Ndrg1 expression was upregulated in the early bell, crown, and root stages in a time-dependent manner. These patterns of expression were similar in Ndrg2, but Ndrg3 and Ndrg4 levels did not change during the developmental stages. Immunofluorescence revealed that strong immunoreactivity against Ndrg1 were detected in differentiated ameloblasts only, not inner enamel epithelium, odontoblasts and ameloblastic cells in defected enamel regions. Alkaline phosphatase and alizarin red s stains along with real time PCR, revealed that Ndrg1 and Ndrg2 were involved in cytodifferentiation and enamel matrix mineralization by selectively regulating amelogenin and ameloblastin genes in SF2 ameloblastic cells. These results suggest that Ndrg may play a crucial functional role in the cytodifferentiation of ameloblasts for amelogenesis.


Assuntos
Amelogênese , Odontogênese , Animais , Ratos , Ameloblastos/metabolismo , Amelogênese/genética , Dente Molar , Proteínas Musculares/metabolismo , Proteínas do Tecido Nervoso/genética , Odontogênese/genética , Proteínas/metabolismo
20.
Acute Crit Care ; 39(1): 169-178, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38303584

RESUMO

BACKGROUND: Studies on the association between pleural effusion (PE) and left ventricular assist devices (LVADs) are limited. This study aimed to examine the characteristics and the clinical impact of PE following LVAD implantation. METHODS: This study is a prospective analysis of patients who underwent LVAD implantation from June 2015 to December 2022. We investigated the prognostic impact of therapeutic drainage (TD) on clinical outcomes. We also compared the characteristics and clinical outcomes between early and late PE and examined the factors related to the development of late PE. RESULTS: A total of 71 patients was analyzed. The TD group (n=45) had a longer ward stay (days; median [interquartile range]: 31.0 [23.0-46.0] vs. 21.0 [16.0-34.0], P=0.006) and total hospital stay (47.0 [36.0-82.0] vs. 31.0 [22.0-48.0], P=0.002) compared to the no TD group (n=26). Early PE was mostly exudate, left-sided, and neutrophil-dominant even though predominance of lymphocytes was the most common finding in late PE. Patients with late PE had a higher rate of reintubation within 14 days (31.8% vs. 4.1%, P=0.004) and longer hospital stays than those without late PE (67.0 [43.0-104.0] vs. 36.0 [28.0-48.0], P<0.001). Subgroup analysis indicated that female sex, low body mass index, cardiac resynchronization therapy, and hypoalbuminemia were associated with late PE. CONCLUSIONS: Compared to patients not undergoing TD, those undergoing TD had a longer hospital stay but not a higher 90-day mortality. Patients with late PE had poor clinical outcomes. Therefore, the correction of risk factors, like hypoalbuminemia, may be required.

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