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1.
Lab Chip ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38836406

ABSTRACT

The parathyroid gland is an endocrine organ that plays a crucial role in regulating calcium levels in blood serum through the secretion of parathyroid hormone (PTH). Hypoparathyroidism is a chronic disease that can occur due to parathyroid defects, but due to the difficulty of creating animal models of this disease or obtaining human normal parathyroid cells, the evaluation of parathyroid functionality for drug development is limited. Although parathyroid-like cells that secrete PTH have recently been reported, their functionality may be overestimated using traditional culture methods that lack in vivo similarities, particularly vascularization. To overcome these limitations, we obtained parathyroid organoids from tonsil-derived mesenchymal stem cells (TMSCs) and fabricated a parathyroid-on-a-chip, capable of simulating PTH secretion based on calcium concentration. This chip exhibited differences in PTH secretion according to calcium concentration and secreted PTH within the range of normal serum levels. In addition, branches of organoids, which are difficult to observe in animal models, were observed in this chip. This could serve as a guideline for successful engraftment in implantation therapies in the future.

2.
Endocrinol Metab (Seoul) ; 39(2): 267-282, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38693817

ABSTRACT

This review article investigates solid organ transplantation-induced osteoporosis, a critical yet often overlooked issue, emphasizing its significance in post-transplant care. The initial sections provide a comprehensive understanding of the prevalence and multifactorial pathogenesis of transplantation osteoporosis, including factors such as deteriorating post-transplantation health, hormonal changes, and the impact of immunosuppressive medications. Furthermore, the review is dedicated to organ-specific considerations in transplantation osteoporosis, with separate analyses for kidney, liver, heart, and lung transplantations. Each section elucidates the unique challenges and management strategies pertinent to transplantation osteoporosis in relation to each organ type, highlighting the necessity of an organ-specific approach to fully understand the diverse manifestations and implications of transplantation osteoporosis. This review underscores the importance of this topic in transplant medicine, aiming to enhance awareness and knowledge among clinicians and researchers. By comprehensively examining transplantation osteoporosis, this study contributes to the development of improved management and care strategies, ultimately leading to improved patient outcomes in this vulnerable group. This detailed review serves as an essential resource for those involved in the complex multidisciplinary care of transplant recipients.


Subject(s)
Organ Transplantation , Osteoporosis , Humans , Organ Transplantation/adverse effects , Osteoporosis/etiology , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Postoperative Complications/etiology
3.
ACS Appl Mater Interfaces ; 16(20): 25825-25835, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38738662

ABSTRACT

Cosmetics and topical medications, such as gels, foams, creams, and lotions, are viscoelastic substances that are applied to the skin or mucous membranes. The human perception of these materials is complex and involves multiple sensory modalities. Traditional panel-based sensory evaluations have limitations due to individual differences in sensory receptors and factors such as age, race, and gender. Therefore, this study proposes a deep-learning-based method for systematically analyzing and effectively identifying the physical properties of cosmetic gels. Time-series friction signals generated by rubbing the gels were measured. These signals were preprocessed through short-time Fourier transform (STFT) and continuous wavelet transform (CWT), respectively, and the frequency factors that change over time were distinguished and analyzed. The deep learning model employed a ResNet-based convolution neural network (CNN) structure with optimization achieved through a learning rate scheduler. The optimized STFT-based 2D CNN model outperforms the CWT-based 2D and 1D CNN models. The optimized STFT-based 2D CNN model also demonstrated robustness and reliability through k-fold cross-validation. This study suggests the potential for an innovative approach to replace traditional expert panel evaluations and objectively assess the user experience of cosmetics.


Subject(s)
Cosmetics , Deep Learning , Fourier Analysis , Gels , Cosmetics/chemistry , Gels/chemistry , Humans , Neural Networks, Computer
5.
BMC Vet Res ; 20(1): 232, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802879

ABSTRACT

BACKGROUND: Human fishing activities have significantly affect environmental concern for marine ecosystems, conservation of marine mammals, and human health. Coastal cetaceans are highly vulnerable to ingestion of fishing gear, bycatching, or entanglement, all of which can be fatal for these animals. In particular, certain coastal dolphins and porpoises are heavily impacted by fishing gear such as angling gear or stownet, as their food often overlap with the target fish species of human fisheries. CASE PRESENTATION: This study presents a case of an Indo-Pacific finless porpoise (Neophocaena phocaenoides) beached on the coast of Jeju Island, Republic of Korea, with ingestion of fishing gear and severe Anisakis infection. Although this species inhabits waters ranging from the Persian Gulf to Taiwan, several stranded carcasses have been reported on Jeju Island in recent years. Post-mortem computed tomography revealed a bundle of four fishing hooks in the forestomach, along with nylon lines and steel lines with connectors, which were assumed to be angling gear for Jeju hairtail (Trichiurus lepturus). Further necroscopic investigation revealed that the forestomach contained a large number of Anisakis spp. (Nematoda: Anisakidae). Histological examination revealed a thickened forestomach wall with pinpoint and volcanic ulcerations, a thickened layer of stratified squamous epithelium, and infiltrated stroma in the squamous epithelium. CONCLUSIONS: This study emphasizes the urgent need to address the impact of fishing activities on marine mammals, marine litter pollution, and the bycatch problem in Korean seawater. In addition, the occurrence of N. phocaenoides in seawater around Jeju Island should be raised in future geographical ecology or veterinary pathology studies and when its distribution is updated.


Subject(s)
Anisakiasis , Anisakis , Porpoises , Animals , Porpoises/parasitology , Republic of Korea , Anisakiasis/veterinary , Anisakiasis/parasitology , Anisakis/isolation & purification , Fisheries , Tomography, X-Ray Computed/veterinary , Male , Postmortem Imaging
6.
Nat Commun ; 15(1): 4663, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38821932

ABSTRACT

Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid ß precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by α-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of α-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by α-syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for α-syn PFF induced pathology deepens our insight about molecular mechanisms of cell-to-cell transmission of pathologic α-syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinson's disease and related α-synucleinopathies.


Subject(s)
Lymphocyte Activation Gene 3 Protein , alpha-Synuclein , alpha-Synuclein/metabolism , alpha-Synuclein/genetics , Humans , Animals , Mice , Antigens, CD/metabolism , Antigens, CD/genetics , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/pathology , Parkinson Disease/metabolism , Parkinson Disease/genetics , Parkinson Disease/pathology , Protein Binding , Amyloid beta-Protein Precursor/metabolism , Amyloid beta-Protein Precursor/genetics , Mice, Knockout , Male , Mice, Inbred C57BL , Female
7.
Curr Res Food Sci ; 8: 100635, 2024.
Article in English | MEDLINE | ID: mdl-38623275

ABSTRACT

Recent studies have shown that the analytic-holistic theory is applicable in sensory science-related areas. Analytic and holistic cognitive style groups have been found to have significantly different perceptions and behaviors within food-related scenarios. These differences were further investigated and identified within the current study, focusing on specific areas of common sensory tests and analyses where analytic and holistic cognitive style groups may differ from one another. Before the main study, 419 volunteers were classified into three groups based on their scores to the Analysis-Holism Scale (AHS). The extreme groups (65 adults for each) were identified as the "analytic" and "holistic" cognitive style groups, respectively. Participants evaluated fruit-flavored beverages and fruit samples for their impression of the intensity or hedonic aspects in the study conducted over two sessions. Each session either employed solely category or line scale for the questions. Analyses focused on the analytic and holistic group comparisons in mean, variance, penalty analysis, and pre- and post-AHS score differences. Results showed that the holistic group exhibited significantly higher mean scores and standard deviations in the hedonic ratings of fruit samples than the analytic group did. Compared to the analytic group, the holistic group showed significantly smaller mean drops in overall liking across the five Just-About-Right (JAR) questions related to flavors or tastes of the mixed-fruit flavored water. A significant difference between the AHS scores measured before and after the sensory evaluation was observed in the holistic group, but not in the analytic group. In conclusion, our findings provide empirical evidence that cognitive styles affect consumer responses to food or beverage samples during sensory evaluation tasks. This implies that sensory professionals may consider these analytic-holistic contrasts while exploring consumer responses to their target samples.

8.
Genes Genomics ; 46(5): 519-529, 2024 May.
Article in English | MEDLINE | ID: mdl-38460098

ABSTRACT

BACKGROUND: GBA1 mutations are the most common genetic risk factor for development of Parkinson's disease (PD). The loss of catalytic activity in GBA1, as well as the reduction of the GBA1 protein in certain cellular compartment, may increase disease progression. However, the mechanisms underlying cellular dysfunction caused by GBA1 deficiency are still mostly unknown. OBJECTIVE: In this study, we focus on the genetic interaction between GBA1 deficiency and PD-causing genes, such as DJ-1, in mitochondrial dysfunction. METHODS: GBA1 knockout (KO) SH-SY5Y cells were used to assess DJ-1 functions against oxidative stress in vitro. The levels of cellular reactive oxygen species were monitored with MitoSOX reagent. The expression of the PARK7 gene was analyzed using the quantitative real-time PCR (qRT-PCR). To understand the mechanism underlying DJ-1 upregulation in GBA1 KO cells, we assess ROS levels, antioxidant protein, and cell viability in GBA1 KO cells with treatment of ROS inhibitor N-acetyl-cysteine or miglustat, which is an inhibitor of glucosylceramide synthase. Dopaminergic degeneration was assessed from Gba1 L444P heterozygous mice mated with Park7 knockout mice. RESULTS: We find that DJ-1 is significantly upregulated in GBA1 KO cells. Elevated levels of DJ-1 are attributed to the transcriptional expression of PARK7 mRNA, but not the inhibition of DJ-1 protein degradation. Because DJ-1 expression is highly linked to oxidative stress, we observe cellular reactive oxygen species (ROS) in GBA1 KO cells. Moreover, several antioxidant gene expressions and protein levels are increased in GBA1 KO cells. To this end, GBA1 KO cells are more susceptible to H2O2-induced cell death. Importantly, there is a significant reduction in dopaminergic neurons in the midbrain from Gba1 L444P heterozygous mice mated with Park7 knockout mice, followed by mild motor dysfunction. CONCLUSION: Taken together, our results suggest that DJ-1 upregulation due to GBA1 deficiency has a protective role against oxidative stress. It may be supposed that mutations or malfunctions in the DJ-1 protein may have disadvantages in the survival of dopaminergic neurons in the brains of patients harboring GBA1 mutations.


Subject(s)
Antioxidants , Neuroblastoma , Parkinson Disease , Humans , Mice , Animals , Reactive Oxygen Species/metabolism , Antioxidants/metabolism , Hydrogen Peroxide , Oxidative Stress , Cell Death/physiology , Mice, Knockout , Protein Deglycase DJ-1/genetics , Protein Deglycase DJ-1/metabolism
9.
J Neurosurg Spine ; 40(5): 570-579, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38335526

ABSTRACT

OBJECTIVE: Short-segment fusion (SSF) is an effective surgical option for appropriately selected patients with de novo degenerative lumbar scoliosis (DNDLS). Considering that DNDLS is frequently accompanied by multisegment degeneration and potential instability across the entire lumbar segments, it is inevitable that unhealthy segments remain after SSF, thereby increasing the potential risk of adjacent-segment disease (ASD) occurrence. Therefore, the authors aimed to identify the risk factors for ASD in patients with DNDLS who underwent SSF. METHODS: This retrospective study included 80 patients with DNDLS (Cobb angle > 10°) who underwent SSF (1 or 2 levels) between December 2010 and July 2018 with a minimum follow-up duration of 5 years. The participants were divided into two groups: ASD and non-ASD. ASD was defined as clinical ASD rather than radiographic ASD. Various patient and operative variables were compared between the groups. Global and regional radiographic parameters (preoperatively and postoperatively) were also compared between the two groups using plain radiography and MRI. Consequently, univariate and multivariate analyses were conducted to identify the risk factors for ASD occurrence. The receiver operating characteristic (ROC) curve was used to calculate the cutoff values. RESULTS: The mean ± SD age was 67.7 ± 7.2 years at the time of SSF, and there were 62 women (77.5%) enrolled in the study. Thirty patients (37.5%) were in the ASD group and 50 patients (62.5%) were in the non-ASD group. The mean time from the surgery to ASD diagnosis was 34.9 ± 28.2 months in ASD group. Thirteen patients required revision surgery at a mean time of 8.8 ± 7.0 months after ASD occurrence. Multivariate logistic regression analysis demonstrated that preoperative disc wedging angle (OR 1.806, 95% CI 1.255-2.598, p = 0.001), presence of facet tropism (defined as ≥ 10° difference between the facet joint angles of the right and left sides) (OR 5.534, 95% CI 1.528-20.040, p = 0.009), and foraminal stenosis ≥ grade 2 (OR 5.935, 95% CI 1.253-28.117, p = 0.025) were significant risk factors for ASD development. The cutoff value of the preoperative disc wedging angle was calculated to be 2.5° using the ROC curve. CONCLUSIONS: Preoperative disc wedging angle ≥ 2.5°, presence of facet tropism, and foraminal stenosis ≥ grade 2 were identified as significant risk factors for ASD development after SSF in patients with DNDLS.


Subject(s)
Lumbar Vertebrae , Scoliosis , Spinal Fusion , Humans , Spinal Fusion/methods , Spinal Fusion/adverse effects , Scoliosis/surgery , Scoliosis/diagnostic imaging , Female , Male , Aged , Risk Factors , Lumbar Vertebrae/surgery , Lumbar Vertebrae/diagnostic imaging , Retrospective Studies , Middle Aged , Postoperative Complications , Intervertebral Disc Degeneration/surgery , Intervertebral Disc Degeneration/diagnostic imaging , Treatment Outcome
10.
World Neurosurg ; 183: e282-e292, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38135150

ABSTRACT

OBJECTIVE: We sought to evaluate the clinical impact of lordosis orientation (LO) on proximal junctional kyphosis (PJK) development in adult spinal deformity surgery. METHODS: This study included 152 patients who underwent low thoracic (T9-T12) to pelvis fusion and were followed up for ≥2 years. In the literature, 6 radiographic parameters representing LO were introduced, such as uppermost instrumented vertebra (UIV) slope, UIV inclination, UIV-femoral angle (UIVFA), thoracolumbar tilt, thoracolumbar slope, and lordosis tilt. Various clinical and radiographic factors including 6 LO parameters were investigated using logistic regression analysis to identify risk factors for PJK. RESULTS: The mean age was 69.4 years, and 136 patients were females (89.5%). PJK developed in 65 patients (42.8%). Multivariate logistic regression analysis revealed that only small postoperative pelvic incidence (PI)-lumbar lordosis (LL) (odds ratio [OR] = 0.962, 95% confidence interval: 0.929-0.996, P = 0.030) and large UIVFA (OR = 1.089, 95% confidence interval: 1.028-1.154, P = 0.004) were significant for PJK development. UIVFA showed significantly positive correlation with pelvic tilt (CC = 0.509), thoracic kyphosis (CC = 0.384), and lordosis distribution index (CC = 0.223). UIVFA was also negatively correlated with sagittal vertical axis (CC = -0.371). However, UIVFA did not correlate with LL, PI-LL, or T1 pelvic angle. CONCLUSIONS: LO significantly increases the risk of PJK development in ASD surgery. Multivariate analysis revealed that smaller postoperative PI-LL and greater UIVFA were significant risk factors for PJK. Surgeons should avoid undercorrection and overcorrection to prevent PJK development.


Subject(s)
Connective Tissue Diseases , Kyphosis , Lordosis , Spinal Fusion , Adult , Female , Animals , Humans , Aged , Male , Lordosis/diagnostic imaging , Lordosis/surgery , Lordosis/complications , Clinical Relevance , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Retrospective Studies , Spinal Fusion/adverse effects , Kyphosis/diagnostic imaging , Kyphosis/surgery , Kyphosis/etiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery
11.
Front Pediatr ; 11: 1308667, 2023.
Article in English | MEDLINE | ID: mdl-38078316

ABSTRACT

Objective: Choledochal cysts are increasingly being diagnosed antenatally. The appropriate time of surgical treatment has the greatest impact on the prognosis of choledochal cyst treatment. The purpose of this study was to compare the clinical outcomes of prenatally diagnosed choledochal cysts in infants according to the surgical treatment timing. Methods: We retrospectively reviewed the medical records of infants who underwent surgery for choledochal cysts with antenatal diagnoses. We investigated each patient's demographic information, type of choledochal cyst, serum liver enzyme levels, and surgical outcomes according to the surgical intervention timing. Results: Between May 2006 and December 2020, 93 infants underwent surgery to treat choledochal cysts; among them, 68 had antenatally suspected choledochal cysts. Of the 68 patients, 21 developed symptoms directly after birth. While 38 patients remained asymptomatic, 9 developed symptoms before operation. To compare surgical outcomes, asymptomatic patients were divided into early (13 cases) and late (25 cases) operation groups based on an age benchmark of 30 days. The early surgical group experienced longer times to resume a full diet (6.0 ± 1.6 vs. 4.5 ± 0.7, p < 0.001) and longer postoperative hospital stays (11 ± 3.9 vs. 7.5 ± 0.8, p < 0.001). Surgical complications occurred in two patients in the early operation group. Minimally invasive surgery was performed in 12 patients in the late operation group. In both groups, postoperative liver function recovered at 6 months, with no significant difference. Conclusion: The results of this study showed longer hospital stays, increased diet durations, and postoperative complications in early surgery patients. However, liver function recovery was not different between the early and late operation groups. Thus, asymptomatic patients should be closely monitored, and we recommend that definitive surgical intervention be postponed until 4 months of age or until weight reaches 7 kg.

12.
bioRxiv ; 2023 Sep 14.
Article in English | MEDLINE | ID: mdl-37745332

ABSTRACT

Mutations in the GBA1 gene have been identified as a prevalent genetic risk factor for Parkinson's disease (PD). GBA1 mutations impair enzymatic activity, leading to lysosomal dysfunction and elevated levels of α-synuclein (α-syn). While most research has primarily focused on GBA1's role in promoting synucleinopathy, emerging evidence suggests that neuroinflammation may be a key pathogenic alteration caused by GBA1 deficiency. To examine the molecular mechanism underlying GBA1 deficiency-mediated neuroinflammation, we generated Gba1 E326K knock-in (KI) mice using the CRISPR/Cas9 technology, which is linked to an increased risk of PD and dementia with Lewy bodies (DLB). In the ventral midbrain and hippocampus of 24-month-old Gba1 E326K KI mice, we found a moderate decline in GBA1 enzymatic activity, a buildup of glucosylceramide, and an increase in microglia density. Furthermore, we observed increased levels of pro-inflammatory cytokines and formation of reactive astrocytes in primary microglia and astrocytes, respectively, cultured from Gba1 E326K KI mice following treatment with pathologic α-syn preformed fibrils (PFF). Additionally, the gut inoculation of α-syn PFF in Gba1 E326K KI mice significantly enhanced the accumulation of Lewy bodies in the dentate gyrus of the hippocampus, accompanied by aggravated neuroinflammation and exacerbated non-motor symptoms. This research significantly enhances our understanding of the Gba1 E326K mutation's involvement in neuroinflammation and the cell-to-cell transmission of pathogenic α-syn in the brain, thereby opening new therapeutic avenues.

13.
Medicina (Kaunas) ; 59(8)2023 Aug 08.
Article in English | MEDLINE | ID: mdl-37629727

ABSTRACT

Backgrounds and objectives: A prevalent concern in anterior cruciate ligament (ACL) reconstruction is postoperative tunnel widening. We hypothesized that employing a curved dilator system (CDS) for femoral tunnel creation can reduce this widening after ACL reconstruction compared to the use of a conventional rigid reamer. Materials and Methods: A retrospective study was conducted involving 56 patients who underwent primary ACL reconstruction between January 2012 and July 2013. The patients were categorized into two groups: the reamer group (n = 28) and CDS group (n = 28). All participants were followed up for a minimum of 2 years. Clinical assessment included the Lachman test and pivot-shift test, and the Lysholm score and subjective International Knee Documentation Committee scores. Radiographic evaluation covered the tunnel widening rate, represented as the ratio of the tunnel diameter 2 years after surgery to the tunnel diameter immediately after surgery, and the ratio (A/B) of femoral tunnel (A) to tibial tunnel (B) diameters at respective time points. Results: No significant disparities were found between the two groups in terms of clinical outcomes. However, the reamer group exhibited a greater femoral tunnel widening rate compared to the CDS group (reamer group vs. CDS group: 142.7 ± 22.0% vs. 128.0 ± 19.0% on the anteroposterior (AP) radiograph and 140.8 ± 14.2% vs. 122.9 ± 13.4% on the lateral radiograph; all p < 0.05). Two years post-operation, the A/B ratio rose in the reamer group (0.96 ± 0.05→1.00 ± 0.05 on the AP radiograph and 0.94 ± 0.03→1.00 ± 0.0.04 on the lateral radiograph; all p < 0.05), while it decreased in the CDS group (0.99 ± 0.02→0.96 ± 0.05 on the AP radiograph and 0.97 ± 0.03→0.93 ± 0.06 on the lateral radiograph; all p < 0.05). Conclusion: The use of CDS for femoral tunnel creation in primary ACL reconstruction provides a potential advantage by limiting tunnel widening compared to the conventional rigid-reamer approach.


Subject(s)
Anterior Cruciate Ligament Reconstruction , Femur , Humans , Retrospective Studies , Femur/surgery , Tibia , Cluster Analysis
14.
Foods ; 12(11)2023 Jun 02.
Article in English | MEDLINE | ID: mdl-37297493

ABSTRACT

In 2020, a single-response-based, valence × arousal circumplex-inspired emotion questionnaire (CEQ) was developed. Using a between-participants design, previous studies have found that a multiple response (MR) condition better discriminated test samples (e.g., written food names) based on their evoked emotions than a single response (SR) condition. This research, comprising Studies 1 and 2, aimed to determine the effect of response conditions (i.e., SR vs. MR) on emotional responses to food image samples, using a within-participants design. In Study 1, 105 Korean participants were asked to select a pair of emotion terms (i.e., SR condition) or select all pairs representing their evoked emotions (i.e., MR condition) from a list of 12 pairs of emotion terms of the CEQ, in response to the 14 food images. Both SR and MR conditions were tested within a remote (online) session. To minimize both a potential carry-over effect of the "within-participants design" and an influence of environmental factors in the remote testing, Study 2 asked 64 U.S. participants to do so over two separated sessions on two different days in a controlled laboratory setting. In both Studies 1 and 2, participants selected the CEQ's emotion-term pairs in the MR condition more frequently than in the SR condition, leading to the MR condition's higher capacity to discriminate test samples. While the configurations of the correspondence analysis biplots drawn in the SR and MR conditions were similar, those in the MR condition were more likely to be similar to the configurations of the principal component analysis biplots drawn from the ratings of valence and arousal for food image samples. In conclusion, this study provides robust empirical evidence that the MR condition can perform better in capturing sample differences in food-evoked emotions, while the SR condition is also effective in characterizing emotional profiles of test samples. Our findings will provide practical insights to sensory professionals, enabling them to effectively leverage the CEQ or its variants when measuring food-evoked emotions.

15.
J Expo Sci Environ Epidemiol ; 33(6): 945-953, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37296232

ABSTRACT

BACKGROUND: Toenails are a promising matrix for chronic metal exposure assessment, but there are currently no standard methods for collection and analysis. Questions remain about sample mass requirements and the extent to which metals measured in this matrix are representative of chronic body burden. OBJECTIVE: This study proposes a method to maximize sample conservation for toenail metals analysis using inductively coupled plasma mass spectrometry (ICP-MS). We demonstrate the reliability of an ~25 mg toenail sample (typically 1-2 clippings) for metals analysis and evaluate the intra-individual variability of multiple metals in this matrix over time in men from the Gulf Long-term Follow-up (GuLF) Study. METHODS: Toenail samples from 123 GuLF Study participants were collected at two visits 3 years apart and analyzed for 18 elements using ICP-MS. Participants with samples exceeding 200 mg at the first visit (n = 29) were selected for triplicate sub-sample analysis. Kendall's coefficient of concordance (W) was used to assess sub-sample reliability and Spearman's correlation coefficients (ρ) were used to evaluate fluctuations in elemental concentrations over time. RESULTS: Results were not reported for Cd, Co, Mo, Sb, and V (detected in <60% of the samples). There was strong agreement among triplicate samples (Kendall's W: 0.72 (Cu)-0.90 (Cu)) across all elements evaluated, moderate correlations of elemental concentrations (Spearman's ρ: 0.21-0.42) over 3 years for As, Ca, Cr, Fe, Pb, Mn, and Zn, and strong correlations (>0.50) for Se, Cu, and Hg. IMPACT STATEMENT: This toenail reliability study found that a low-mass (~25 mg) toenail sample (1-2 clippings) is suitable for the determination of most elements using ICP-MS and helps to increase the analytical capacity of limited toenail biospecimens collected in cohort studies. The results highlight differences in the suitability of toenails for chronic metal exposure assessment by element and underscore the need to consider intra-person variability, especially when comparing results across studies. We also provide recommendations for analytical standardization and the partitioning of the total collected toenail sample into multiple analytic sub-samples for future studies using toenail biospecimen for multiple assays.


Subject(s)
Mercury , Trace Elements , Male , Humans , Nails/chemistry , Reproducibility of Results , Metals/analysis , Mercury/analysis , Biomarkers/analysis , Trace Elements/analysis
16.
Cell Stem Cell ; 30(7): 973-986.e11, 2023 07 06.
Article in English | MEDLINE | ID: mdl-37339636

ABSTRACT

Human induced pluripotent stem cells (hiPSCs) offer advantages for disease modeling and drug discovery. However, recreating innate cellular pathologies, particularly in late-onset neurodegenerative diseases with accumulated protein aggregates including Parkinson's disease (PD), has been challenging. To overcome this barrier, we developed an optogenetics-assisted α-synuclein (α-syn) aggregation induction system (OASIS) that rapidly induces α-syn aggregates and toxicity in PD hiPSC-midbrain dopaminergic neurons and midbrain organoids. Our OASIS-based primary compound screening with SH-SY5Y cells identified 5 candidates that were secondarily validated with OASIS PD hiPSC-midbrain dopaminergic neurons and midbrain organoids, leading us to finally select BAG956. Furthermore, BAG956 significantly reverses characteristic PD phenotypes in α-syn preformed fibril models in vitro and in vivo by promoting autophagic clearance of pathological α-syn aggregates. Following the FDA Modernization Act 2.0's emphasis on alternative non-animal testing methods, our OASIS can serve as an animal-free preclinical test model (newly termed "nonclinical test") for the synucleinopathy drug development.


Subject(s)
Induced Pluripotent Stem Cells , Neuroblastoma , Parkinson Disease , Humans , alpha-Synuclein/genetics , alpha-Synuclein/metabolism , Dopaminergic Neurons/metabolism , Induced Pluripotent Stem Cells/metabolism , Neuroblastoma/metabolism , Neuroblastoma/pathology , Optogenetics , Parkinson Disease/genetics
17.
Arch Osteoporos ; 18(1): 61, 2023 05 02.
Article in English | MEDLINE | ID: mdl-37129630

ABSTRACT

In this population-based retrospective cohort study, exercising before and after the diagnosis of type 2 diabetes was significantly associated with lower risk of fractures. This result suggested that exercising might be effective in reducing fracture risk. PURPOSE: Patients with diabetes have a significantly higher risk of fractures. We aimed to investigate the association between exercise and fracture risk in new-onset type 2 diabetes. METHODS: This retrospective cohort study using the Korean National Health Insurance Service database included 170,148 patients with new-onset type 2 diabetes who underwent two cycles of health checkup between 2009-2012 and 2011-2014. The patients were classified into four groups (non-exercising, newly exercising, previously exercising, and continuously exercising) and followed up until the date of fracture, death, or December 31, 2018. Hip fractures, vertebral fractures, and any fractures were defined using diagnostic codes. RESULTS: The proportions of non-exercising, newly exercising, previously exercising, and continuously exercising patients were 65.1%, 15.7%, 10.9%, and 8.3%, respectively. Continuously exercising patients showed the lowest risk for fractures, followed by newly exercising patients using the non-exercising group as a reference. The adjusted hazard ratios (95% confidence intervals) for hip fracture, vertebral fracture, and any fracture were 0.69 (0.50-0.94), 0.73 (0.63-0.84), and 0.90 (0.83-0.97), respectively, in the continuously exercising group and 0.76 (0.61-0.95), 0.85 (0.76-0.94), and 0.93 (0.88-0.98) in the newly exercising group. The risk was lower in patients who lost less than 5% of their body weight than in those who lost 5% or more. CONCLUSION: Exercising was associated with lower risk of fractures in newly diagnosed diabetes. However, exercise accompanied by excessive weight loss may not have a significant association with a lower risk of fractures.


Subject(s)
Diabetes Mellitus, Type 2 , Hip Fractures , Spinal Fractures , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Retrospective Studies , Hip Fractures/epidemiology , Hip Fractures/complications , Spinal Fractures/complications , Risk
18.
Foods ; 12(9)2023 Apr 26.
Article in English | MEDLINE | ID: mdl-37174331

ABSTRACT

This study aimed to determine whether and how three demographic factors-age group, gender, and consumption frequency-affect texture perception and liking of two staple foods-cooked rice and wheat bread. In total, 346 adults evaluated three cooked rice and four wheat bread samples in terms of three (hardness, stickiness, and chewiness) and four textural attributes (hardness, moistness, chewiness, and softness), respectively, on both 9-point intensity and 5-point Just-About-Right (JAR) scales. Liking of test samples was also rated on 9-point hedonic scales. Age group and gender differed in mean ratings, standard deviations, and JAR responses regarding textural attribute intensity and overall liking of test samples, while the effect of consumption frequency was minimal in this regard. Significant contributors of textural attributes to overall liking of cooked rice and wheat bread differed with age group, gender, and consumption frequency. Effects of age group, gender, and consumption frequency on texture perception and overall liking also varied with test samples. This study provides agricultural and food systems professionals with systematic evidence of how textural attribute perception and liking of foods can change based on demographics and test samples.

19.
Korean J Radiol ; 24(5): 465-475, 2023 05.
Article in English | MEDLINE | ID: mdl-37056157

ABSTRACT

OBJECTIVE: To evaluate the feasibility of ultrasound shear wave elastography (SWE) for predicting hepatic fibrosis and native liver outcomes in patients with biliary atresia. MATERIALS AND METHODS: This prospective study included 33 consecutive patients with biliary atresia (median age, 8 weeks [interquartile range, 6-10 weeks]; male:female ratio, 15:18) from Severance Children's Hospital between May 2019 and February 2022. Preoperative (within 1 week from surgery) and immediate postoperative (on postoperative days [PODs] 3, 5, and 7) ultrasonographic findings were obtained and analyzed, including the SWE of the liver and spleen. Hepatic fibrosis, according to the METAVIR score at the time of Kasai portoenterostomy and native liver outcomes during postsurgical follow-up, were compared and correlated with imaging and laboratory findings. Poor outcomes were defined as intractable cholangitis or liver transplantation. The diagnostic performance of SWE in predicting METAVIR F3-F4 and poor hepatic outcomes was analyzed using receiver operating characteristic (ROC) analyses. RESULTS: All patients were analyzed without exclusion. Perioperative advanced hepatic fibrosis (F3-F4) was associated with older age and higher preoperative direct bilirubin and SWE values in the liver and spleen. Preoperative liver SWE showed a ROC area of 0.806 and 63.6% (7/11) sensitivity and 86.4% (19/22) specificity at a cutoff of 17.5 kPa for diagnosing F3-F4. The poor outcome group included five patients with intractable cholangitis and three undergoing liver transplantation who showed high postoperative liver SWE values. Liver SWE on PODs 3-7 showed ROC areas of 0.783-0.891 for predicting poor outcomes, and a cutoff value of 10.3 kPa for SWE on POD 3 had 100% (8/8) sensitivity and 73.9% (17/23) specificity. CONCLUSION: Preoperative liver SWE can predict advanced hepatic fibrosis, and immediate postoperative liver SWE can predict poor native liver outcomes in patients with biliary atresia.


Subject(s)
Biliary Atresia , Cholangitis , Elasticity Imaging Techniques , Child , Humans , Male , Female , Infant , Biliary Atresia/diagnostic imaging , Biliary Atresia/surgery , Elasticity Imaging Techniques/methods , Prospective Studies , Liver Cirrhosis/diagnostic imaging
20.
Osteoporos Sarcopenia ; 9(1): 38-39, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37082358
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