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STUDY DESIGN: Retrospective study. OBJECTIVES: To investigate the incidence and risk factors of mechanical failure (MF) following anterior column realignment (ACR) in patients with severe degenerative sagittal imbalance (DSI). SUMMARY OF BACKGROUND DATA: Considering the biomechanical properties of the procedure, ACR may increase the risk of MF, including proximal junctional kyphosis (PJK) and rod fracture (RF). However, this issue has been poorly documented in the literature. METHODS: We included patients aged ≥60 years with severe DSI radiographically defined by pelvic incidence (PI) - lumbar lordosis (LL) ≥20° undergoing ≥5-level fusion, including the sacrum. PJK was defined radiographically as a proximal junctional angle (PJA)>28° plus Δ PJA of>22°. RF was evaluated at ACR levels performed. Clinical and radiographic variables were compared to identify the risk factors for PJK and RF, then multivariate analysis was performed by combining PJK and RF into a single composite outcome of MF. RESULTS: We included a total of 147 patients in the final study cohort. The mean age was 70.3 years, and there were 126 women (90.6%). The median fusion length was 8 levels. After surgery, PI-LL was corrected from 48.1° to 4.3°. MF developed in 49 patients (33.3%); PJK in 41 (27.9%), RF in 11 (7.5%), and both PJK and RF in 3 (2.0%) patients. Multivariate analyses revealed that osteoporosis (odds ratio [OR]=2.361, 95% confidence interval [CI]=1.270 - 5.590, P=0.048) and an increased number of ACR levels (OR=1.762, 95% CI=1.039 - 3.587, P=0.036) were significant risk factors for MF. CONCLUSION: A considerable number of patients (33.3%) developed MF after deformity correction using ACR procedures. Therefore, appropriate surgical strategies are necessary to prevent MF in patients undergoing deformity correction using ACR, with special attention to the risk factors we identified here.
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BACKGROUND: Despite numerous studies identifying risk factors for proximal junctional failure (PJF), risk factors for recurrent PJF (R-PJF) are still not well established. Therefore, we aimed to identify the risk factors for R-PJF following adult spinal deformity (ASD) surgery. METHODS: Among 479 patients who underwent ≥5-level fusion surgery for ASD, the focus was on those who experienced R-PJF at any time or did not experience R-PJF during a follow-up duration of ≥1 year. PJF was defined as a proximal junctional angle (PJA) ≥28° plus a difference in PJA ≥22° or performance of revision surgery regardless of PJA degree. The patients were divided into 2 groups according to R-PJF development: no R-PJF and R-PJF groups. Risk factors were evaluated focusing on patient, surgical, and radiographic factors at the index surgery as well as at the revision surgery. RESULTS: Of the 60 patients in the final study cohort, 24 (40%) experienced R-PJF. Significant risk factors included greater postoperative sagittal vertical axis (OR = 1.044), overcorrection relative to age-adjusted pelvic incidence-lumbar lordosis (PI-LL; OR = 7.794) at the index surgery, a greater total sum of the proximal junctional kyphosis severity scale (OR = 1.145), and no use of the upper instrumented vertebra cement (OR = 5.494) at the revision surgery. CONCLUSIONS: We revealed that the greater postoperative sagittal vertical axis and overcorrection relative to age-adjusted pelvic incidence-lumbar lordosis at the index surgery, a greater proximal junctional kyphosis severity scale score, and no use of upper instrumented vertebra cement at the revision surgery were significant risk factors for R-PJF. CLINICAL RELEVANCE: To reduce the risk of R-PJF after ASD surgery, avoiding under- and overcorrection during the initial surgery is recommended. Additionally, close assessment of the severity of PJF with timely intervention is crucial, and cement augmentation should be considered during revision surgery.
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Quantifying the formation and decomposition of amyloid is a crucial issue in the development of new drugs and therapies for treating amyloidosis. The current technologies for grasping amyloid formation and decomposition include fluorescence analysis using thioflavin-T, secondary structure analysis using circular dichroism, and image analysis using atomic force microscopy or transmission electron microscopy. These technologies typically require spectroscopic devices or expensive nanoscale imaging equipment and involve lengthy analysis, which limits the rapid screening of amyloid-degrading drugs. In this study, we introduce a technology for rapidly assessing amyloid decomposition using capillary flow-based paper (CFP). Amyloid solutions exhibit gel-like physical properties due to insoluble denatured polymers, resulting in a shorter flow distance on CFP compared to pure water. Experimental conditions were established to consistently control the flow distance based on a hen-egg-white lysozyme amyloid solution. It was confirmed that as amyloid is decomposed by trypsin, the flow distance increases on the CFP. Our method is highly useful for detecting changes in the gel properties of amyloid solutions within a minute, and we anticipate its use in the rapid, large-scale screening of anti-amyloid agents in the future.
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Amiloide , Muramidase , Proteólise , Amiloide/metabolismo , AnimaisRESUMO
INTRODUCTION: Apical periodontitis, mainly caused by bacterial infection in the tooth pulp, is often accompanied by abscess, periapical inflammation, and alveolar bone loss. Recently, Lancefieldella rimae was detected in the root canals of patients with apical periodontitis. Here, we investigated whether L. rimae is associated with bone resorption. METHODS: L. rimae was anaerobically cultured and heat-killed (HKLr). A mouse calvarial implantation model was used to determine the bone resorption in vivo. Committed osteoclasts prepared C57BL/6 wild-type or Toll-like receptor 2 (TLR2)-deficient mice were differentiated into mature osteoclasts in the presence or absence of HKLr. The mRNA expression of tartrate-resistant acid phosphatase (TRAP), ATPase H+ transporting V0 subunit D2 (Atp6v0d2), cathepsin K, IL-6, TNF-α, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was quantified using real-time reverse transcription-polymerase chain reaction. The protein levels of c-FOS and NFATc1 were determined by Western blot analysis. RESULTS: Implantation of HKLr onto the mouse calvaria induced the bone destruction with an increase of TRAP-positive areas. While HKLr enhanced the differentiation of osteoclasts, this effect was not observed in TLR2-deficient osteoclasts. HKLr dose-dependently increased the mRNA expression of genes associated with osteoclast differentiation including TRAP, Atp6v0d2, and cathepsin K. In addition, HKLr enhanced the expression of c-FOS and NFATc1, which are important transcription factors for osteoclast differentiation. Moreover, HKLr increased the expression of IL-6 and TNF-α. CONCLUSION: L. rimae induces bone resorption by enhancing osteoclast differentiation through the TLR2 signaling pathway, implying that L. rimae is a causative agent responsible for the alveolar bone resorption accompanying apical periodontitis.
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BACKGROUND CONTEXT: While numerous studies have been conducted on proximal junctional failure (PJF), the clinical significance of acute and delayed PJF remains poorly understood. PURPOSE: The primary object of this study is to investigate the risk factors separately for acute and delayed PJF. Secondly, we aim to assess the incidence of each failure mode and their clinical consequences in relation to acute and delayed PJF. STUDY DESIGN/SETTING: Retrospective comparative study. PATIENT SAMPLE: Patients aged ≥60 years who underwent deformity correction with ≥5-level fusion to sacrum. OUTCOME MEASURES: Risk factor, failure modes, and patient-reported outcome measure (PROM). METHODS: Acute PJF is defined as PJF occurring within 6 months, while delayed PJF occurring after 6 months. Risk factors were analyzed by comparing various clinical and radiographic parameters among 3 groups: no, acute, and delayed PJF groups. The failure modes, including soft tissue failure, vertebral fracture, fixation failure, and myelopathy, were compared among these groups. The clinical subsequences after PJF development were evaluated by assessing the change in proximal junctional angle (PJA), revision rate, and patient-reported outcome measure (PROM). RESULTS: A study cohort of 363 patients was included in the analysis. Among them, 156 patients experienced PJF, with 87 patients (55.8%) in the acute PJF group and 69 patients (44.2%) in the delayed PJF group. Multivariate analyses showed that older age (Odds ratio [OR] = 1.057, 95% confidence interval [CI] = 1.002-1.118), osteoporosis (OR=2.149, 95% CI = 1.074-4.300), high American Society of Anesthesiology ASA score (OR=2.150, 95% CI = 1.089-4.245), and overcorrection relative to the age-adjusted pelvic incidence - lumbar lordosis target (OR=4.031, 95% CI = 1.962-8.280) were identified as risk factors for the development of acute PJF. On the other hand, a high body mass index (OR=1.150, 95% CI = 1.049-1.251) and an uppermost instrumented vertebra located at ≤T10 (OR=2.267, 95% CI = 1.205-4.268) were found to be associated with delayed occurrence of PJF. No radiographic parameters were found to be related to the development of delayed PJF. In terms of failure modes, vertebral fracture and fixation failure were more commonly observed in acute PJF, while soft tissue failure and myelopathy were more predominant in delayed PJF. The clinical course was more aggressive in the acute PJF group compared to the delayed PJF group, as evidenced by a greater increase in PJA, a higher revision rate, and worse PROM. CONCLUSIONS: This study demonstrated different risk factors between the acute and delayed PJF. It was found that overcorrection relative to the age-adjusted PI-LL target increased the risk of acute PJF, but had no impact on the development of delayed PJF. Therefore, a different surgical strategy needs to be established to mitigate both acute and delayed PJF.
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Hg2+ is a highly toxic heavy metal ion that poses serious risks to human health and the environment. Due to its tendency to accumulate, it can easily enter the human body through the food chain, making it crucial to develop detection sensors that mimic real environmental conditions. To achieve this, our study employed a surface-enhanced Raman scattering (SERS) sensor using two strategies. First, we designed a highly selective probe by optimizing the probe and reporter DNA strands to bind Hg2+ within a thymine-thymine mismatch. Second, we used the double coffee ring effect to concentrate the optimized probe DNA. These two strategies greatly enhanced the SERS signal, resulting in a sensor with exceptional sensitivity, a low detection limit of 208.71 fM, and superior selectivity for Hg2+. The practical application of the sensor was demonstrated by successfully detecting Hg2+ in drinking water, tap water, canned tuna, and tuna sashimi. Additionally, the experimental results were presented in a pizza-shaped SERS mapping image, allowing users to estimate Hg2+ concentrations through color, providing a user-friendly and intuitive method for data comprehension and analysis. Our study presents a promising approach for sensitive and reliable Hg2+ detection, with potential implications for environmental monitoring and food safety.
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Técnicas Biossensoriais , DNA , Limite de Detecção , Mercúrio , Análise Espectral Raman , Mercúrio/análise , Mercúrio/química , Análise Espectral Raman/métodos , Técnicas Biossensoriais/métodos , DNA/química , DNA/análise , Humanos , Contaminação de Alimentos/análise , Água Potável/análise , Nanopartículas Metálicas/química , Poluentes Químicos da Água/análise , Ouro/química , Animais , Monitoramento Ambiental/métodosRESUMO
Background/Objectives: There is no solid consensus regarding which lowest instrumented vertebra (LIV) selection criterion is best to prevent distal adding-on (DA) after adolescent idiopathic scoliosis (AIS) surgery. This study aims to search out the LIV selection criteria in the literature and to compare the ability of each LIV selection criterion to prevent DA in patients with AIS. Methods: Patients who underwent thoracic fusion for AIS of Lenke type 1A or 1B were included in this study. Nine criteria for LIV selection were found in a literature review. For each patient, whether the postoperative actual location of LIV was met with the suggested locations of the LIV was assessed. The preventive ability of nine criteria against DA was evaluated using logistic regression analysis. The patients who met the LIV selection criteria but developed DA were investigated. Results: The study cohort consisted of 145 consecutive patients with a mean age of 14.8 years. The criteria of Suk (OR = 0.267), Parisini (OR = 0.230), Wang (OR = 0.289), and Qin (OR = 0.210) showed a significantly decreased risk of DA if the LIV selection criterion was chosen at each suggested landmark. As the additional levels were fused, there was no statistically significant benefit in further reducing the risk of DA. Among the patients who met each criterion, the incidence of DA was lower in criteria by Takahashi (5.9%), Qin (7.1%), and King (7.4%) than the others. Conclusions: Qin's criterion, using the substantially touching vertebra concept, has the highest preventive ability against DA development. Extending the instrumentation further distal to this suggested LIV criterion did not add further benefit.
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STUDY DESIGN: Retrospective study. OBJECTIVE: We sought to compare surgical outcomes according to baseline balance statuses in elderly patients with degenerative sagittal imbalance (DSI). SUMMARY OF BACKGROUND: Although optimal sagittal correction has been emphasized for good surgical outcomes, the effect of the state of preoperative balance on surgical outcome has been adequately described at present. METHODS: Patients aged ≥60 years with DSI who underwent ≥5-level fusion to the sacrum were included. Among them, only those who postoperatively achieved the optimal age-adjusted pelvic incidence (PI) - lumbar lordosis (LL) target were included in this study. Study participants were divided into two groups according to their preoperative sagittal vertical axis (SVA): compensatory balance (SVA <5 cm, group CB) and decompensation (SVA ≥5 cm, group D). Comparisons between the two groups were performed using the chi-squared test or Fisher's exact test for categorical variables and the independent t- test or Wilcoxon rank- sum test for continuous variables. RESULTS: A total of 156 patients whose postoperative sagittal alignment matched the age-adjusted PI-LL target constituted the study cohort. There were 59 patients in group CB and 97 patients in group D. Mean follow-up duration was 50.0 months after surgery. Immediate postoperatively, sacral slope and SVA were significantly greater in group D than in group CB. At last follow-up, the SVA was significantly greater in group D than in group CB (43.6 vs. 22.7 mm), while no significant differences were found in other sagittal parameters. The Oswestry disability index and Scoliosis Research Society -22 scores at the last follow-up were significantly worse in group D than in group CB. CONCLUSION: The SVA tended to experience less correction postoperatively, with evidence of further deterioration during follow-up in group D than in group CB. This suboptimal correction of SVA may contribute to the inferior clinical outcomes encountered in group D relative to group CB. Therefore, we recommend correction of PI-LL as close as possible to the lower limit of the suggested PI-LL target range in patients with evidence of preoperative decompensation.
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OBJECTIVE: To determine the clinical impact of the baseline sagittal imbalance severity in patients with adult spinal deformity (ASD). METHODS: We retrospectively reviewed patients who underwent ≥ 5-level fusion including the pelvis, for ASD with a ≥ 2-year follow-up. Using the Scoliosis Research Society-Schwab classification system, patients were classified into 3 groups according to the severity of the preoperative sagittal imbalance: mild, moderate, and severe. Postoperative clinical and radiographic results were compared among the 3 groups. RESULTS: A total of 259 patients were finally included. There were 42, 62, and 155 patients in the mild, moderate, and severe groups, respectively. The perioperative surgical burden was greatest in the severe group. Postoperatively, this group also showed the largest pelvic incidence minus lumbar lordosis mismatch, suggesting a tendency towards undercorrection. No statistically significant differences were observed in proximal junctional kyphosis, proximal junctional failure, or rod fractures among the groups. Visual analogue scale for back pain and Scoliosis Research Society-22 scores were similar across groups. However, severe group's last follow-up Oswestry Disability Index (ODI) scores significantly lower than those of the severe group. CONCLUSION: Patients with severe sagittal imbalance were treated with more invasive surgical methods along with increased the perioperative surgical burden. All patients exhibited significant radiological and clinical improvements after surgery. However, regarding ODI, the severe group demonstrated slightly worse clinical outcomes than the other groups, probably due to relatively higher proportion of undercorrection. Therefore, more rigorous correction is necessary to achieve optimal sagittal alignment specifically in patients with severe baseline sagittal imbalance.
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Bulbar dysfunction in amyotrophic lateral sclerosis (ALS) significantly affects daily life, leading to weight loss and reduced survival. Methods for evaluating bulbar dysfunction, including videofluoroscopic swallowing studies and the bulbar component of the ALS Functional Rating Scale-Revised (ALSFRS-R), have been employed; however, Korean-specific tools are lacking. The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) comprehensively evaluates bulbar symptoms. This study aimed to develop and validate the Korean version of the CNS-BFS (K-CNS-BFS) to assess bulbar dysfunction in Korean patients with ALS. Twenty-seven patients with ALS were recruited from a tertiary hospital in South Korea based on revised El Escorial criteria. Demographic, clinical, and measurement data were collected. The K-CNS-BFS was evaluated for reliability and validity. Reliability assessment revealed strong internal consistency (Cronbach alpha) for the K-CNS-BFS subscales and total score. Test-retest reliability showed significant correlation. Content validity index was excellent, and convergent validity demonstrated significant correlations between the K-CNS-BFS and relevant measures. Discriminant validity was observed between the K-CNS-BFS and motor/respiratory subscores of the ALSFRS-R. Construct validity demonstrated significant correlations between the K-CNS-BFS subscales and total score. This is the first study to investigate the reliability and validity of the Korean version of the CNS-BFS, which showed consistent and reliable scores that correlated with tests for bulbar or general dysfunction. The K-CNS-BFS effectively measured bulbar dysfunction similar to the original CNS-BFS. The K-CNS-BFS is a reliable and valid tool for assessing bulbar dysfunction in patients with ALS in South Korea.
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Esclerose Lateral Amiotrófica , Índice de Gravidade de Doença , Humanos , Masculino , Feminino , República da Coreia , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/diagnóstico , Idoso , AdultoRESUMO
BACKGROUND AND OBJECTIVES: Appropriate correction relative to the age-adjusted sagittal alignment target reduces the proximal junctional failure (PJF) risk. Nonetheless, a considerable number of patients suffer from PJF despite optimal correction. The aim of this study was to identify the risk factors of PJF that occurs despite optimal correction relative to the sagittal age-adjusted score (SAAS) in adult spinal deformity surgery. METHODS: Patients aged 60 years or older with adult spinal deformity who underwent ≥5-level fusion to the sacrum were initially screened. Among them, only patients who achieved optimal sagittal correction relative to the SAAS were included in the study. Optimal correction was defined as the SAAS point between -1 and +1. Various clinical and radiographic factors were compared between the PJF and no PJF groups and were further evaluated using multivariate analysis. RESULTS: The final study cohort comprised 127 patients. The mean age was 67 years, and there were 111 women (87.4%). A mean of total fusion length was 7.2. PJF occurred in 42 patients (33.1%), while 85 patients (66.9%) did not develop PJF. Multivariate analysis showed that a high body mass index (odds ratio [OR] = 1.153, 95% CI = 1.027-1.295, P = .016), a higher lordosis distribution index (LDI) (OR = 1.024, 95% CI = 1.003-1.045, P = .022), and no use of hook fixation (OR = 9.708, 95% CI = 1.121-76.923, P = .032) were significant risk factors of PJF development. In the receiver operating characteristic curve analysis, the cutoff value for the LDI was calculated as 61.0% (area under the curve = 0.790, P < .001). CONCLUSION: PJF developed in a considerable portion of patients despite optimal correction relative to the age-adjusted alignment. The risk factors of PJF in this patient group were high body mass index, high LDI exceeding 61%, and no use of hook fixation. PJF could be further decreased by properly managing these risk factors along with optimal sagittal correction.
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STUDY DESIGN: Retrospective study. OBJECTIVES: To determine the ideal pelvic incidence (PI) - lumbar lordosis (LL) range to prevent pelvic tilt (PT) undercorrection while avoiding PI-LL overcorrection following adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND: PI-LL and PT are the important sagittal parameters to be restored to an adequate range by surgery. Ideal PI-LL target without causing PI-LL overcorrection and PT undercorrection has not been documented. METHODS: We included patients with ASD undergoing ≥5-level fusion including the sacrum. Receiver operating characteristic (ROC) curve analysis was performed to calculate the lower limit of the ideal PI-LL without causing PI-LL overcorrection and the upper limit of ideal PI-LL without causing PT undercorrection. The calculated ideal PI-LL was validated in terms of proximal junctional kyphosis and failure (PJK and PJF) rates and clinical outcomes. Analyses were performed according to age subgroups (<70 and ≥70 y). RESULTS: In total, 426 patients were included in the study. Female patients were predominant (85.4%), with a mean age of 69.8 years. The lower limits of PI-LL were calculated as 4.9° for all patients, 2.3° for patients aged <70 years, and 7.9° for patients aged ≥70 years. Meanwhile, the upper limits of PI-LL were calculated as 12.7° for all patients, 12.5° for patients aged <70 years, and 13.3° for patients aged ≥70 years. There were no significant differences in the PJK and PJF rates among the new three PI-LL groups. Clinical outcomes were significantly better in patients with the ideal PI-LL group than those in patients with overcorrection or undercorrection groups for all age groups. CONCLUSION: The ideal PI-LL correction target without adversely impacting PT and PI-LL was calculated at 2.3°-12.5° for patients aged <70 years and 7.9°-13.3° for patients aged ≥70 years. These guideline parameters may help ensure optimal clinical outcomes without increasing the risk of PJK/F.
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BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.
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Vacinas contra COVID-19 , COVID-19 , Hospitalização , Miastenia Gravis , SARS-CoV-2 , Vacinação , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/complicações , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Idoso , SARS-CoV-2/isolamento & purificação , Adulto , Prognóstico , Unidades de Terapia Intensiva , Respiração ArtificialRESUMO
Intracellular cargo trafficking is a highly regulated process responsible for transporting vital cellular components to their designated destinations. This intricate journey has been a central focus of cellular biology for many years. Early investigations leaned heavily on biochemical and genetic approaches, offering valuable insight into molecular mechanisms of cellular trafficking. However, while informative, these methods lack the capacity to capture the dynamic nature of intracellular trafficking. The advent of fluorescent protein tagging techniques transformed our ability to monitor the complete lifecycle of intracellular cargos, advancing our understanding. Yet, a central question remains: How do these cargos manage to navigate through traffic challenges, such as congestion, within the crowded cellular environment? Fluorescence-based imaging, though valuable, has inherent limitations when it comes to addressing the aforementioned question. It is prone to photobleaching, making long-term live-cell imaging challenging. Furthermore, they render unlabeled cellular constituents invisible, thereby missing critical environmental information. Notably, the unlabeled majority likely exerts a significant influence on the observed behavior of labeled molecules. These considerations underscore the necessity of developing complementary label-free imaging methods to overcome the limitations of fluorescence imaging or to integrate them synergistically.In this Account, we outline how label-free interference-based imaging has the potential to revolutionize the study of intracellular traffic by offering unprecedented levels of detail. We begin with a brief introduction to our previous findings in live-cell research enabled by interferometric scattering (iSCAT) microscopy, showcasing its aptitude and adeptness in elucidating intricate nanoscale intracellular structures. As we delved deeper into our exploration, we succeeded in the label-free visualization of the entire lifespan of nanoscale protein complexes known as nascent adhesions (NAs) and the dynamic events associated with adhesions within living cells. Our continuous efforts have led to the development of Dynamic Scattering-particle Localization Interference Microscopy (DySLIM), a generalized concept of cargo-localization iSCAT (CL-iSCAT). This label-free, high-speed imaging method, armed with iSCAT detection sensitivity, empowers us to capture quantitative and biophysical insights into cargo transport, providing a realistic view of the intricate nanoscale logistics occurring within living cells. Our in vivo studies demonstrate that intracellular cargos regularly contend with substantial traffic within the crowded cellular environment. Simultaneously, they employ inherent strategies for efficient cargo transport, such as collective migration and hitchhiking, to enhance overall transport ratesâintriguingly paralleling the principle and practice of urban traffic management. We also highlight the synergistic benefits of combining DySLIM with chemical-selective fluorescent methods. This Account concludes with a "Conclusions and Outlook" section, outlining promising directions for future research and developments, with a particular emphasis on the functional application of iSCAT live-cell imaging. We aim to inspire further investigation into the efficient transport strategies employed by cells to surmount transportation challenges, shedding light on their significance in cellular phenomena.
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Imagem Óptica , Humanos , Animais , Transporte Biológico , Microscopia de FluorescênciaRESUMO
Many studies sought to demonstrate the association between smoking and fracture risk. However, the correlation between smoking and fractures remains controversial. This study aimed to examine the impact of smoking and smoking cessation on the occurrence of fractures using prospective nationwide cohort data. We enrolled those who underwent a National Health Insurance Service (NHIS) health checkup in 2009-2010 who had a previous health checkup 4-year prior (2005-2006). The study population of 4,028,559 subjects was classified into three groups (non-smoker, smoking cessation, current smoker). The study population was also analyzed according to fracture type (all fractures, vertebral fracture, hip fracture). Lastly, the smoking cessation group and current smoker group were divided into four subgroups based on a lifetime smoking amount cut-off of 20 pack-years (PY). Multivariate-adjusted hazard ratios (HRs) of fracture were examined through a Cox proportional hazards model. After multivariable adjustment, non-smokers showed the lowest risk of fracture (HR = 0.818, CI 0.807-0.828, p < 0.0001) and smoking cessation significantly lowered the risk of fracture (HR 0.938, 95% CI 0.917-0.959, p < 0.0001) compared to current smokers. Regardless of 20PY, all smoking cessation subgroups showed significantly less risk of fractures than current smokers with ≥ 20PYs. Smoking increases the risk of fracture, and smoking cessation lowers the risk of fracture.
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Fraturas Ósseas , Abandono do Hábito de Fumar , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Adulto , Idoso , Fatores de Risco , Fumar/efeitos adversos , Estudos Prospectivos , Modelos de Riscos Proporcionais , Estudos de Coortes , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/prevenção & controleRESUMO
The precise and reversible detection of hydrogen sulfide (H2S) at high humidity condition, a malodorous and harmful volatile sulfur compound, is essential for the self-assessment of oral diseases, halitosis, and asthma. However, the selective and reversible detection of trace concentrations of H2S (≈0.1 ppm) in high humidity conditions (exhaled breath) is challenging because of irreversible H2S adsorption/desorption at the surface of chemiresistors. The study reports the synthesis of Fe-doped CuO hollow spheres as H2S gas-sensing materials via spray pyrolysis. 4 at.% of Fe-doped CuO hollow spheres exhibit high selectivity (response ratio ≥ 34.4) over interference gas (ethanol, 1 ppm) and reversible sensing characteristics (100% recovery) to 0.1 ppm of H2S under high humidity (relative humidity 80%) at 175 °C. The effect of multi-valent transition metal ion doping into CuO on sensor reversibility is confirmed through the enhancement of recovery kinetics by doping 4 at.% of Ti- or Nb ions into CuO sensors. Mechanistic details of these excellent H2S sensing characteristics are also investigated by analyzing the redox reactions and the catalytic activity change of the Fe-doped CuO sensing materials. The selective and reversible detection of H2S using the Fe-doped CuO sensor suggested in this work opens a new possibility for halitosis self-monitoring.
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Asthma and allergic rhinitis (AR) are 2 of the most common chronic inflammatory disorders and they appear to be on the rise. Current pharmacotherapy effectively controls symptoms but does not alter the underlying pathophysiology. Allergen immunotherapy (AIT) is an evidence-based therapy for asthma and AR and has been recognized as the only therapeutic method that actually modifies the allergic disease process. There is a lack of objective markers that accurately and reliably reflect the therapeutic benefits of AIT. A biomarker indicating patients that would benefit most from AIT would be invaluable. Eosinophilic inflammation is a cardinal feature of many allergic diseases. Biomarkers that accurately reflect this inflammation are needed to better diagnose, treat, and monitor patients with allergic disorders. This review examines the current literature regarding AIT's effects on eosinophilic inflammation and biomarkers that may be used to determine the extent of these effects.
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Thiabendazole (TBZ) is a benzimidazole; owing to its potent antimicrobial properties, TBZ is extensively employed in agriculture as a fungicide and pesticide. However, TBZ poses environmental risks, and excessive exposure to TBZ through various leakage pathways can cause adverse effects in humans. Therefore, a method must be developed for early and sensitive detection of TBZ over a range of concentrations, considering both human and environmental perspectives. In this study, we used silver nanopillar structures (SNPis) and Au@Ag bimetallic nanoparticles (BNPs) to fabricate a BNP@SNPi substrate. This substrate exhibited a broad reaction surface with significantly enhanced surface-enhanced Raman scattering hotspots, demonstrating excellent Raman performance, along with high reproducibility, sensitivity, and selectivity for TBZ detection. Ultimately, the BNP@SNPi substrate successfully detected TBZ across a wide concentration range in samples of tap water, drinking water, juice, and human serum, with respective limits of detection of 146.5, 245.5, 195.6, and 219.4 pM. This study highlights BNP@SNPi as a promising sensor platform for TBZ detection in diverse environments and contributes to environmental monitoring and bioanalytical studies.
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Nanopartículas Metálicas , Praguicidas , Humanos , Tiabendazol/química , Análise Espectral Raman/métodos , Reprodutibilidade dos Testes , Nanopartículas Metálicas/químicaRESUMO
OBJECTIVE: This study aimed to investigate the long-term effects and functional outcomes of androgen suppression therapy using leuprorelin among Korean patients with spinal and bulbar muscular atrophy (SBMA). METHODS: This observational study enrolled patients with genetically confirmed SBMA who provided informed consent. Leuprorelin was administered via subcutaneous injection every 12 weeks. The primary outcome measure was the change in total Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS) scores. RESULTS: A total of 48 SBMA patients were evaluated in this study. Among them, 39 patients underwent androgen suppression therapy over a 3-year period. The total SBMAFRS score decreased from 41.72 ± 5.55 to 36.74 ± 7.74 (p < 0.001) in patients who completed their treatment. The subgroup with a baseline SBMAFRS score of ≥ 42 had a significantly lower decline in SBMAFRS score than did those with a baseline SBMAFRS score of ≤ 41. We determined that at a baseline, SBMAFRS cutoff value of 41.5 could predict good prognosis, with a corresponding area under the curve of 0.689. CONCLUSION: Despite androgen suppression therapy, all enrolled participants exhibited a decrease in the overall SBMAFRS score. However, those with a baseline SBMAFRS of ≥ 42 showed a mild decrease in scores, indicating a more favorable prognosis. These findings suggest that a higher baseline motor function was a key prognostic indicator in SBMA treatment and that initiating early leuprorelin treatment in patients with high baseline function may lead to good clinical outcomes.
Assuntos
Leuprolida , Humanos , Leuprolida/uso terapêutico , Leuprolida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Feminino , Idoso , Adulto , Antagonistas de Androgênios/uso terapêutico , Atrofia Muscular Espinal/tratamento farmacológico , Atrofia Bulboespinal Ligada ao X/tratamento farmacológico , Índice de Gravidade de DoençaRESUMO
Coronaviruses are single-stranded RNA viruses with high mutation rates. Although a diagnostic method for coronaviruses has been developed, variants appear rapidly. Low test accuracy owing to single-point mutations is one of the main factors in the failure to prevent the early spread of coronavirus infection. Although reverse transcription-quantitative polymerase chain reaction can detect coronavirus infection, it cannot exclude the possibility of false positives, and an additional multiplexing kit is needed to discriminate single nucleotide polymorphism (SNP) variants. Therefore, in this study, we introduced a new nucleic acid amplification method to determine whether an infected person has a SNP mutation using a lateral flow assay (LFA) as a point-of-care test. Unlike traditional DNA amplification methods, direct insertion into rolling circle amplification amplifies the target genes without false amplification. After SNP-selective nucleic acid amplification, nuclease enzymes are used to make double-stranded DNA fragments that the LFA can detect, where specific mismatched DNA is found and cleaved to show different signals when a SNP-type is present. Therefore, wild- and SNP-type variants can be selectively detected. In this study, the limit of detection was 400 aM for viral RNA, and we successfully identified a dominant SNP variant selectively. Clinical tests were also conducted.