RESUMO
Various vaccine platforms were developed and deployed against the COVID-19 disease. The Fc-mediated functions of IgG antibodies are essential in the adaptive immune response elicited by vaccines. However, the long-term changes of protein subunit vaccines and their combinations with messenger RNA (mRNA) vaccines are unknown. A total of 272 serum and plasma samples were collected from individuals who received first to third doses of the protein subunit Medigen, the mRNA (BNT, Moderna), or the adenovector AstraZeneca vaccines. The IgG subclass level was measured using enzyme-linked immunosorbent assay, and Fc-N glycosylation was measured using liquid chromatography coupled to tandem mass spectrometry. Antibody-dependent-cellular-phagocytosis (ADCP) and complement deposition (ADCD) of anti-spike (S) IgG antibodies were measured by flow cytometry. IgG1 and 3 reached the highest anti-S IgG subclass level. IgG1, 2, and 4 subclass levels significantly increased in mRNA- and Medigen-vaccinated individuals. Fc-glycosylation was stable, except in female BNT vaccinees, who showed increased bisection and decreased galactosylation. Female BNT vaccinees had a higher anti-S IgG titer than that of males. ADCP declined in all groups. ADCD was significantly lower in AstraZeneca-vaccinated individuals. Each vaccine produced specific long-term changes in Fc structure and function. This finding is critical when selecting a vaccine platform or combination to achieve the desired immune response.
Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunoglobulina G , SARS-CoV-2 , Vacinas de Subunidades Antigênicas , Vacinas de mRNA , Humanos , Imunoglobulina G/sangue , Feminino , Anticorpos Antivirais/sangue , Masculino , COVID-19/prevenção & controle , COVID-19/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Adulto , Pessoa de Meia-Idade , Vacinas contra COVID-19/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/genética , Vacinas de Subunidades Antigênicas/administração & dosagem , Glicosilação , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Idoso , RNA Mensageiro/genética , Adulto Jovem , Vacinas de Subunidades ProteicasRESUMO
Background: Anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) are both considered to be efficacious surgical procedures for treating cervical spondylosis in patients with or without compression myelopathy. This updated systematic review and meta-analysis aimed to compare the outcomes of these procedures for the treatment of cervical degenerative disc disease (DDD) at two contiguous levels. Methods: The PubMed, EMBASE, and Cochrane CENTRAL databases were searched up to 1 May 2023. Studies comparing the outcomes between CDA and ACDF in patients with two-level cervical DDD were eligible for inclusion. Primary outcomes were surgical success rates and secondary surgery rates. Secondary outcomes were scores on the Neck Disability Index (NDI) and Visual Analogue Scale (VAS) for neck and arm pain, as well as the Japanese Orthopaedic Association (JOA) score for the severity of cervical compression myelopathy and complication rates. Results: In total, eight studies (two RCTs, four retrospective studies, and two prospective studies) with a total of 1155 patients (CDA: 598; ACDF: 557) were included. Pooled results revealed that CDA was associated with a significantly higher overall success rate (OR, 2.710, 95% CI: 1.949-3.770) and lower secondary surgery rate (OR, 0.254, 95% CI: 0.169-0.382) compared to ACDF. In addition, complication rates were significantly lower in the CDA group than in the ACDF group (OR, 0.548, 95% CI: 0.326 to 0.919). CDA was also associated with significantly greater improvements in neck pain VAS than ACDF. No significant differences were found in improvements in the arm VAS, NDI, and JOA scores between the two procedures. Conclusions: CDA may provide better postoperative outcomes for surgical success, secondary surgery, pain reduction, and postoperative complications than ACDF for treating patients with two-level cervical DDD.
RESUMO
Background: In this investigation, we aimed to understand the influence of oral probiotic supplementation on the vaginal microbiota of women preparing for assisted reproductive technology (ART) procedures. Given the importance of a healthy microbiome for reproductive success, this study sought to explore how probiotics might alter the bacterial composition in the vaginal environment. Methods: We recruited a cohort of 30 women, averaging 37 years of age (ranging from 31 to 43 years), who were scheduled to undergo ART. Using 16S ribosomal RNA (rRNA) sequencing, we meticulously analyzed the vaginal microbiota composition before and after the administration of oral probiotic supplements. Results: Our analysis identified 17 distinct microorganisms, including 8 species of Lactobacillus. Following probiotic supplementation, we observed subtle yet notable changes in the vaginal microbiota of some participants. Specifically, there was a decrease in Gardnerella abundance by approximately 20%, and increases in Lactobacillus and Bifidobacterium by 10% and 15%, respectively. Additionally, we noted a significant reduction in the Firmicutes/Bacteroidetes (F/B) ratio in the probiotic group, indicating potential shifts in the overall bacterial composition. Conclusions: These preliminary findings suggest that oral probiotic supplementation can induce significant changes in the vaginal microbiota of middle-aged women undergoing ART, potentially improving their overall bacterial profile. Future studies should consider a larger sample size and a narrower age range to validate these results. Investigating factors related to female hormone production could also provide deeper insights. Understanding the effects of probiotics on the vaginal microbiota in patients with ovarian aging may lead to personalized interventions and better reproductive outcomes.
RESUMO
Osteoarthritis is more prevalent than any other form of arthritis and is characterized by the progressive mechanical deterioration of joints. Glucosamine, an amino monosaccharide, has been used for over fifty years as a dietary supplement to alleviate osteoarthritis-related discomfort. Silibinin, extracted from milk thistle, modifies the degree of glycosylation of target proteins, making it an essential component in the treatment of various diseases. In this study, we aimed to investigate the functional roles of glucosamine and silibinin in cartilage homeostasis using the TC28a2 cell line. Western blots showed that glucosamine suppressed the N-glycosylation of the gp130, EGFR, and N-cadherin proteins. Furthermore, both glucosamine and silibinin differentially decreased and increased target proteins such as gp130, Snail, and KLF4 in TC28a2 cells. We observed that both compounds dose-dependently induced the proliferation of TC28a2 cells. Our MitoSOX and DCFH-DA dye data showed that 1 µM glucosamine suppressed mitochondrial reactive oxygen species (ROS) generation and induced cytosol ROS generation, whereas silibinin induced both mitochondrial and cytosol ROS generation in TC28a2 cells. Our JC-1 data showed that glucosamine increased red aggregates, resulting in an increase in the red/green fluorescence intensity ratio, while all the tested silibinin concentrations increased the green monomers, resulting in decreases in the red/green ratio. We observed increasing subG1 and S populations and decreasing G1 and G2/M populations with increasing amounts of glucosamine, while increasing amounts of silibinin led to increases in subG1, S, and G2/M populations and decreases in G1 populations in TC28a2 cells. MTT data showed that both glucosamine and silibinin induced cytotoxicity in TC28a2 cells in a dose-dependent manner. Regarding endoplasmic reticulum stress, both compounds induced the expression of CHOP and increased the level of p-eIF2α/eIF2α. With respect to O-GlcNAcylation status, glucosamine and silibinin both reduced the levels of O-GlcNAc transferase and hypoxia-inducible factor 1 alpha. Furthermore, we examined proteins and mRNAs related to these processes. In summary, our findings demonstrated that these compounds differentially modulated cellular proliferation, mitochondrial and cytosol ROS generation, the mitochondrial membrane potential, the cell cycle profile, and autophagy. Therefore, we conclude that glucosamine and silibinin not only mediate glycosylation modifications but also regulate cellular processes in human chondrocytes.
Assuntos
Condrócitos , Glucosamina , Homeostase , Fator 4 Semelhante a Kruppel , Espécies Reativas de Oxigênio , Silibina , Glucosamina/farmacologia , Glucosamina/metabolismo , Humanos , Silibina/farmacologia , Glicosilação/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fator 4 Semelhante a Kruppel/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Cartilagem/metabolismo , Cartilagem/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Osteoartrite/metabolismo , Osteoartrite/tratamento farmacológicoRESUMO
As women age, oocytes are susceptible to a myriad of dysfunctions, including mitochondrial dysfunction, impaired DNA repair mechanisms, epigenetic alterations, and metabolic disturbances, culminating in reduced fertility rates among older individuals. Ferredoxin (FDX) represents a highly conserved iron-sulfur (Fe-S) protein essential for electron transport across multiple metabolic pathways. Mammalian mitochondria house two distinct ferredoxins, FDX1 and FDX2, which share structural similarities and yet perform unique functions. In our investigation into the regulatory mechanisms governing ovarian aging, we employed a comprehensive multi-omics analysis approach, integrating spatial transcriptomics, single-cell RNA sequencing, human ovarian pathology, and clinical biopsy data. Previous studies have highlighted intricate interactions involving excessive lipid peroxide accumulation, redox-induced metal ion buildup, and alterations in cellular energy metabolism observed in aging cells. Through a multi-omics analysis, we observed a notable decline in the expression of the critical gene FDX1 as ovarian age progressed. This observation prompted speculation regarding FDX1's potential as a promising biomarker for ovarian aging. Following this, we initiated a clinical trial involving 70 patients with aging ovaries. These patients were administered oral nutritional supplements consisting of DHEA, ubiquinol CoQ10, and Cleo-20 T3 for a period of two months to evaluate alterations in energy metabolism regulated by FDX1. Our results demonstrated a significant elevation in FDX1 levels among participants receiving nutritional supplementation. We hypothesize that these nutrients potentiate mitochondrial tricarboxylic acid cycle (TCA) activity or electron transport chain (ETC) efficiency, thereby augmenting FDX1 expression, an essential electron carrier in metabolic pathways, while concurrently mitigating lipid peroxide accumulation and cellular apoptosis. In summary, our findings underscore the potential of nutritional intervention to enhance in vitro fertilization outcomes in senescent cells by bolstering electron transport proteins, thus optimizing energy metabolism and improving oocyte quality in aging women.
Assuntos
Envelhecimento , Suplementos Nutricionais , Ferredoxinas , Mitocôndrias , Ovário , Ubiquinona , Feminino , Humanos , Ovário/metabolismo , Ferredoxinas/metabolismo , Mitocôndrias/metabolismo , Adulto , Ubiquinona/análogos & derivados , Ubiquinona/administração & dosagem , Ubiquinona/farmacologia , Redes e Vias Metabólicas , Metabolismo Energético , Pessoa de Meia-IdadeRESUMO
Antibody detection is the critical first step for tracking the spread of many diseases including COVID-19. Lateral flow immunoassay (LFIA) is the most commonly used method for rapid antibody detection because it is easy-to-use and inexpensive. However, LFIA has limited sensitivity when gold nanoparticles (AuNPs) are used as the signals. In this study, the endospores of Bacillus subtilis were used in combination with AuNP in a LFIA to detect antibodies. The endospores serve as a signal amplifier. The detection limit was about 10-8 M for anti-beta galactosidase antibody detection whereas the detection limit of conventional LFIA is about 10-6 M. Furthermore, the proposed methods have no additional user steps compared with the traditional LFIA. This method, therefore, improved the sensitivity 100-fold without compromising any advantages of LFIA. We believe that the proposed method will be useful for detection of antibodies against HIV, Zika virus, SARS-CoV-2, and so on.
Assuntos
Bacillus subtilis , Ouro , Limite de Detecção , Nanopartículas Metálicas , Bacillus subtilis/imunologia , Imunoensaio/métodos , Ouro/química , Nanopartículas Metálicas/química , Humanos , Esporos Bacterianos/imunologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/imunologia , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , Zika virus/imunologiaRESUMO
Various vaccine platforms were developed and deployed against the COVID-19 disease. The Fc-mediated functions of IgG antibodies are essential in the adaptive immune response elicited by vaccines. However, the long-term changes of protein subunit vaccines and their combinations with mRNA vaccines are unknown. A total of 272 serum and plasma samples were collected from individuals who received first to third doses of the protein subunit Medigen, the mRNA (BNT), or the adenovector AstraZeneca vaccines. The IgG subclass level was measured using enzyme-linked immunosorbent assay, and Fc-N glycosylation was measured using LC-MS/MS. Antibody-dependent phagocytosis (ADCP) and complement deposition (ADCD) of anti-spike (S) IgG antibodies were measured. IgG1 and 3 reached the highest anti-S IgG subclass level. IgG1, 2, and 4 subclass levels significantly increased in mRNA- and Medigen-vaccinated individuals. Fc-glycosylation was stable, except in female BNT vaccinees, who showed increased bisection and decreased galactosylation. Female BNT vaccinees had a higher anti-S IgG titer than that of males. ADCP declined in all groups. ADCD increased in Medigen-vaccinated individuals after the third dose. Each vaccine produced specific long-term changes in Fc structure and function. This finding is critical when selecting a vaccine platform or combination to achieve the desired immune response.
RESUMO
Cuproptosis is a recently discovered mode of cell death that has garnered attention due to its association with various diseases. However, the intricate genetic relationship between cuproptosis and ovarian aging has remained largely unexplored. This study aimed to bridge this knowledge gap by leveraging data sets related to ovarian aging and cuproptosis. Through comprehensive bioinformatics analyses, facilitated by R software, we uncovered FDX1 as a potential cuproptosis-related gene with relevance to ovarian aging. To gain insights into FDX1's role, we conducted spatial transcriptome analyses in the ovaries of both young and aged female mice. These experiments revealed a significant reduction in FDX1 expression in the aging group compared to the young group. To substantiate these findings at the genetic level, we turned to clinical infertility biopsies. Impressively, we observed consistent results in biopsies from elderly infertile patients, reinforcing the link between FDX1 and ovarian aging. Moreover, we delved into the pharmacogenomics of ovarian cell lines and discovered that FDX1 expression levels were intricately associated with heightened sensitivity to specific small molecule drugs. This observation suggests that modulating FDX1 could potentially be a strategy to influence drug responses in ovarian-related therapies. In sum, this study marks a pioneering effort in identifying FDX1 as a cuproptosis-related gene implicated in ovarian aging. These findings hold substantial promise, not only in shedding light on the underlying mechanisms of ovarian aging but also in positioning FDX1 as a potential diagnostic biomarker and therapeutic target. With further research, FDX1 could play a pivotal role in advancing precision medicine and therapies for ovarian-related conditions.
RESUMO
Bisphosphonates have been associated with a decreased risk of revision surgery after total joint arthroplasty of the hip or knee (TJA) because of their effects on decreased periprosthetic bone loss and prosthetic migration. However, the results in the early literature are inconsistent, and the influence of bisphosphonates on associated complications and subsequent TJA remains unknown. This study investigated the association between the use of bisphosphonates and the risk of adverse outcomes after primary TJA. This matched cohort study utilized the National Health Insurance Research Database in Taiwan to identify patients who underwent primary TJA over a 15-year period (January 2000-December 2015 inclusive). Study participants were further categorized into two groups, bisphosphonate users and nonusers, using propensity score matching. The Kaplan-Meier curve analysis and adjusted hazard ratios (aHRs) of revision surgery, adverse outcomes of primary surgery and subsequent TJA were calculated using Cox regression analysis. This study analyzed data from 6485 patients who underwent total hip arthroplasty (THA) and 20,920 patients who underwent total knee arthroplasty (TKA). The risk of revision hip and knee arthroplasty was significantly lower in the bisphosphonate users than in the nonusers (aHR, 0.54 and 0.53, respectively). Furthermore, the risk of a subsequent total joint arthroplasty, adverse events and all-cause mortality were also significantly reduced in the bisphosphonate users. This study, involving a large cohort of patients who underwent primary arthroplasties, revealed that bisphosphonate treatment may potentially reduce the risk of revision surgery and associated adverse outcomes. Furthermore, the use of bisphosphonates after TJA is also associated with a reduced need for subsequent arthroplasty.Research Registration Unique Identifying Number (UIN): ClinicalTrials.gov Identifier-NCT05623540 ( https://clinicaltrials.gov/show/NCT05623540 ).
Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Difosfonatos , Humanos , Feminino , Masculino , Difosfonatos/uso terapêutico , Difosfonatos/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/estatística & dados numéricos , Idoso , Pessoa de Meia-Idade , Artroplastia de Quadril/efeitos adversos , Estudos de Coortes , Reoperação/estatística & dados numéricos , Taiwan/epidemiologia , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Resultado do TratamentoRESUMO
In addition to substituting low-price and low-quality materials for high-quality materials at the food processing stage, many dishonest businesses risk adulterating chemical materials in products to reduce production costs or increase product flavor with chemical synthesis spices. As a result, the risks to food safety are increased. Most safety management and certification regulations proceed with on-site examination or sampling inspection. As current certification systems lack complete tracking and real-time certification processes, they cannot comprehensively check foods' processing and production processes and contents. Hence, food safety problems sway consumers' trust and confidence in certification systems. This study intends to improve the agricultural processing end's current food traceability certification system. Adding the design of raw material total quantity control provides a complete and sound real-time certification mechanism for citizens and businesses to assure consumer rights.
Assuntos
Manipulação de Alimentos , Inocuidade dos Alimentos , Gestão da Segurança , Certificação , EspeciariasRESUMO
Triplet transitions of light-emitting materials, including rose bengal, tris(2-phenylpyridine)iridium(III) [Ir(ppy)3], tris(1-phenylisoquinoline)iridium(III) [Ir(piq)3], and bis[2-(4,6-difluorophenyl)pyridinato-C2,N](picolinato)iridium(III) (FIrpic), were studied using step-scan time-resolved Fourier-transform near-infrared spectroscopy. The samples were excited to their singlet excited states by a 355 nm laser and then underwent efficient conversions/crossings to their triplet manifolds. For rose bengal, a transient absorption band appeared at 9400 cm-1, attributed to the T3 â T1 transition based on the corresponding time evolution and the theoretical calculations. For Ir(ppy)3, Ir(piq)3, and FIrpic, the most intense bands were observed at 7700, 7500, and 7500 cm-1 and assigned to T7 â T1, T6 â T1, and T6 â T1 transitions, respectively. For Ir(ppy)3, the most intense band involved transitions between different triplet metal-to-ligand charge transfer (3MLCT) states, while for Ir(piq)3 and FIrpic, they involved a metal center to 3MLCT transition. These T1 states were assigned to 3MLCT.
RESUMO
There is a need for non-pharmaceutical intervention methods that can prevent and indicate the risk of airborne disease spread. In this study, we developed a nonwoven mat based on the polyphenol gallic acid, which can inhibit pathogens growth and also indicate pathogen levels in the surrounding environment. Using nuclear magnetic resonance, Fourier-transform infrared spectroscopy, and high-performance liquid chromatography, we characterized this novel gelatin-based nonwoven mat and investigated the mechanism governing its ability to indicate pathogen levels. We demonstrated that the incorporation of gallic acid serves a vital role in indicating the presence of bacteria, causing the nonwoven mat to change in color from white to brown. We have proposed a plausible mechanism for this color change behavior based on a reaction of gallic acid with components excreted by bacteria, including glutamate, valine, and leucine. The concentrations of these components reflect the bacterial counts, enabling a real-time indication of pathogen levels in the surrounding air. In summary, the nonwoven mat presented herein can serve as an excellent antibacterial agent and as an indicator of nearby bacteria for fabricating personal protection equipment like filtration mask.
RESUMO
Doxorubicin (Dox) is a potent anticancer agent, but its associated organ toxicity, including nephrotoxicity, restricts clinical applications. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 inhibitor, has been shown to slow the progression of kidney disease in patients with and without diabetes. However, the effect of DAPA to counteract Dox-induced nephrotoxicity remains uncertain. Therefore, in this study, we aimed to elucidate the effects of DAPA in mitigating Dox-induced nephrotoxicity. We analyzed the Taiwan National Health Insurance Database to evaluate the incidence of renal failure among breast cancer patients receiving Dox treatment compared to those without. After adjusting for age and comorbidities, we found that the risk of renal failure was significantly higher in Dox-treated patients (incidence rate ratio, 2.45; confidence interval, 1.41-4.26; p = 0.0014). In a parallel study, we orally administered DAPA to Sprague-Dawley rats for 6 weeks, followed by Dox for 4 weeks. DAPA ameliorated Dox-induced glomerular atrophy, renal fibrosis, and dysfunction. Furthermore, DAPA effectively suppressed Dox-induced apoptosis and reactive oxygen species production. On a cellular level, DAPA in HK-2 cells mitigated Dox-mediated suppression of the endothelial NOS pathway and reduced Dox-induced activities of reactive oxygen species and apoptosis-associated proteins. DAPA improved Dox-induced apoptosis and renal dysfunction, suggesting its potential utility in preventing nephrotoxicity in patients with cancer undergoing Dox treatment.
Assuntos
Nefropatias , Insuficiência Renal , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Ratos , Animais , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Ratos Sprague-Dawley , Doxorrubicina/efeitos adversos , Nefropatias/induzido quimicamente , Insuficiência Renal/induzido quimicamente , ApoptoseRESUMO
Compared to other techniques, RNA sequencing (RNA-Seq) has the advantage of having details of the expression abundance of all transcripts in a single run. In this study, we used RNA-Seq to monitor the maturity and dynamic characteristics of in vitro hepatocyte cultures. Hepatocytes, including mature hepatocytes and small hepatocytes, were analyzed in vitro using RNA-Seq and quantitative polymerase chain reaction (qPCR). The results demonstrated that the gene expression profiles measured by RNA-Seq showed a similar trend to the expression profiles measured by qPCR, and can be used to infer the success of in vitro hepatocyte cultures. The results of the differential analysis, which compared mature hepatocytes against small hepatocytes, revealed 836 downregulated and 137 upregulated genes. In addition, the success of the hepatocyte cultures could be explained by the gene list screened from the adopted gene enrichment test. In summary, we demonstrated that RNA-Seq could become an effective method for monitoring the whole transcriptome of hepatocyte cultures and provide a more comprehensive list of factors related to the differentiation of small hepatocytes into mature hepatocytes. This monitoring system not only shows high potential in medical applications but may also be a novel method for the clinical diagnosis of liver-related diseases.
Assuntos
Hepatócitos , Transcriptoma , Ratos , Animais , RNA-Seq , Hepatócitos/metabolismo , Análise de Sequência de RNA , Células Cultivadas , FígadoRESUMO
Colorectal cancer (CRC) is one of the types of cancers with a high incidence and is ranked the 3rd among men and 2nd among women worldwide. The purpose of this study was to investigate the correlation between non-SMC condensin I complex subunit G (NCAPG) and the prognosis of CRC and its function in CRC cells. The expression of NCAPG in colorectal tissues and cells was detected by immunoblotting and immunohistochemistry. Kaplan-Meier analysis was used to analyze the correlation between NCAPG and CRC prognosis. RNAi technology was used to investigate how NCAPG inhibition affected the proliferation and migration of CRC cells. Overexpression of NCAPG was positively correlated with several clinicopathologic characteristics, including T stage (P = 0.0198), M stage (P = 0.0005), and TNM stage (P < 0.0001). Kaplan-Meier analysis showed that the overexpression of NCAPG was also negatively correlated with disease-free survival and overall survival. In the culture of CRC cells, the knockdown of NCAPG inhibited the proliferation, migration, and invasion of the cells. Meanwhile, it was also found that NCAPG knockdown could interfere with G2/M-G1 transition in the cell cycle, resulting in the inhibition of cell proliferation. The overexpression of NCAPG may serve as a candidate biomarker for CRC prognosis. NCAPG is also a potential therapeutic target for CRC.
Assuntos
Carcinogênese , Neoplasias Colorretais , Masculino , Humanos , Feminino , Linhagem Celular Tumoral , Prognóstico , Interferência de RNA , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Ciclo Celular/metabolismoRESUMO
OBJECTIVES: This study aimed to investigate the relationship between depression in older nursing home residents and family caregivers' (FCGs) depressive status and reasons for involvement with residents. DESIGN: This study employed a cross-sectional design. SETTING: Eight nursing homes in northern Taiwan. PARTICIPANTS: A total of 139 older resident-FCG pairs were recruited. MEASUREMENTS: Depression was measured with the Geriatric Depression Scale-Short Form for nursing home residents and the Center for Epidemiologic Studies Depression Scale-Short Form for family members. Depression and demographic data were collected with face-to-face interviews. The meaning ascribed to caregivers' nursing home visits was calibrated using the Family Meaning of Nursing-Home Visits scale. Multiple logistic regression was used to understand the factors related to residents' depressive symptoms. RESULTS: Depressive symptoms were present in 58.3% of the nursing home residents (n = 81). Depressive status of family members (Chi-square = 1.46, p = 0.23) or family's visiting frequency (Chi-square = 1.64, p = 0.44) did not differ between residents with or without depressive symptoms. Factors associated with an increased risk of residents having depressive symptoms were age, self-perceived health status, and having a caregiver motivated to visit to assuage their guilt. CONCLUSIONS: Visiting a family member to assuage their guilt was the only caregiver variable associated with depressive symptoms for nursing home residents. This finding suggests that developing interventions to improve personal relationships between nursing home residents and family members might facilitate the emotional support of caregivers and psychological support for older nursing home residents in Taiwan.
Assuntos
Família , Casas de Saúde , Humanos , Idoso , Estudos Transversais , Família/psicologia , Nível de Saúde , TaiwanRESUMO
BACKGROUND/PURPOSE: Complex arthroplasties for periacetabular metastatic lesions can result in complications including infection and prosthesis loosening owing to poor bone quality. A new surgical protocol has been developed as a joint-sparing surgery to avoid complications after arthroplasties. The main surgical steps are: (a) conservative and accurate tumor resection with aid of 3D printing model-assisted preoperative resection simulation and preparation of pre-contour plate, (b) reconstruction with structural bone graft through the sandwich technique for augmentation of subchondral bone. METHODS: This retrospective study consisted of 6 patients (5 with metastatic bone tumors and one with multiple myeloma). The pelvic bone resection as defined by Enneking and Dunham were typed I + II in 2 patients and type II in 4 patients. The medical records, images, musculoskeletal tumor society (MSTS) score and visual analogue scale (VAS) were used for evaluation. RESULTS: The mean operative time was 234 minutes, and the average surgical blood loss was 1408 mL. The mean follow-up period was 21 months. The mean VAS significantly decreased at postoperative 1-week and 1-year follow-up. There were no intraoperative or early postoperative complications. The median MSTS score during the final follow-up was 26 points (range, 14-28 points). Except for one case who experienced severe joint destruction, all the other five cases were classified as excellent or good (>15). CONCLUSION: With precise tumor resection and reconstruction with sandwich procedure, the joint-sparing surgery can be performed in selected patients with metastatic periacetabular tumors.
Assuntos
Neoplasias Ósseas , Humanos , Estudos Retrospectivos , Neoplasias Ósseas/cirurgia , Complicações Pós-Operatórias , Impressão Tridimensional , Resultado do TratamentoRESUMO
Effectively handling the limited number of surgery operating rooms equipped with expensive equipment is a challenging task for hospital management such as reducing the case-time duration and reducing idle time. Improving the efficiency of operating room usage via reducing the idle time with better scheduling would rely on accurate estimation of surgery duration. Our model can achieve a good prediction result on surgery duration with a dozen of features. We have found the result of our best performing department-specific XGBoost model with the values 31.6 min, 18.71 min, 0.71, 28% and 27% for the metrics of root-mean-square error (RMSE), mean absolute error (MAE), coefficient of determination (R2), mean absolute percentage error (MAPE) and proportion of estimated result within 10% variation, respectively. We have presented each department-specific result with our estimated results between 5 and 10 min deviation would be more informative to the users in the real application. Our study shows comparable performance with previous studies, and the machine learning methods use fewer features that are better suited for universal usability.
RESUMO
OBJECTIVE: To use deep learning to predict the probability of triangular fibrocartilage complex (TFCC) injury in patients' MRI scans. METHODS: We retrospectively studied medical records over 11 years and 2 months (1 January 2009-29 February 2019), collecting 332 contrast-enhanced hand MRI scans showing TFCC injury (143 scans) or not (189 scans) from a general hospital. We employed two convolutional neural networks with the MRNet (Algorithm 1) and ResNet50 (Algorithm 2) framework for deep learning. Explainable artificial intelligence was used for heatmap analysis. We tested deep learning using an external dataset containing the MRI scans of 12 patients with TFCC injuries and 38 healthy subjects. RESULTS: In the internal dataset, Algorithm 1 had an AUC of 0.809 (95% confidence interval-CI: 0.670-0.947) for TFCC injury detection as well as an accuracy, sensitivity, and specificity of 75.6% (95% CI: 0.613-0.858), 66.7% (95% CI: 0.438-0.837), and 81.5% (95% CI: 0.633-0.918), respectively, and an F1 score of 0.686. Algorithm 2 had an AUC of 0.871 (95% CI: 0.747-0.995) for TFCC injury detection and an accuracy, sensitivity, and specificity of 90.7% (95% CI: 0.787-0.962), 88.2% (95% CI: 0.664-0.966), and 92.3% (95% CI: 0.763-0.978), respectively, and an F1 score of 0.882. The accuracy, sensitivity, and specificity for radiologist 1 were 88.9, 94.4 and 85.2%, respectively, and for radiologist 2, they were 71.1, 100 and 51.9%, respectively. CONCLUSIONS: A modified MRNet framework enables the detection of TFCC injury and guides accurate diagnosis.
RESUMO
Metastasis is a leading cause of cancer-related deaths. Hence, the discovery of more reliable metastasis-related biomarkers is crucial to improve the survival rate of cancer patients. W3 is an aptamer previously produced by the subtractive cell-SELEX using metastatic colorectal cancer cells as target cells and non-metastatic cells as negative cells. In this study, we aimed to evaluate whether the target molecule of W3 can potentially act as a metastatic biomarker. First, we obtained two cell subpopulations with different expression levels of the target molecule by W3-based cell sorting. Subsequently, we demonstrated that W3high cells have a higher metastatic potential than W3low cells both in vitro and in vivo. Further, immunohistochemical analysis revealed that W3 target expression is positively associated with metastasis and poor prognosis of CRC patients. Using mass spectrometry (MS) combined with pull-down, we identified that Ephrin type-A receptor 2 (EphA2) is the target of W3. EphA2's potential as a metastatic predictor was demonstrated by capturing W3-positive circulating tumor cells from CRC patients using a W3 probe. Based on these results, we put forward a stratagem for cell-SELEX-based biomarker discovery: selecting an aptamer through subtractive cell-SELEX towards the phenotype of interest; evaluating the functional phenotype of the target molecule by aptamer-based target cell sorting and analysis of clinical samples; and identifying the aptamer's target molecule using MS and aptamer-based target enrichment. This stratagem not only shortens the time for the clinical application of aptamers but also enables a more targeted and efficient discovery of biomarkers.