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Objectives: FDXR encodes the mitochondrial ferredoxin reductase, which is associated with auditory neuropathy spectrum disorder (ANSD) and optic atrophy. Only two studies have described FDXRrelated hearing loss. The auditory rehabilitation outcomes of this disease entity have not been investigated, and the pathophysiologic mechanism is not well elucidated. Here we report a hearingimpaired subject with co-segregation of the FDXR variant and post-synaptic type ANSD, who underwent cochlear implantation (CI) with favorable outcomes. We suggest a possible pathophysiologic mechanism of adult-onset ANSD via mitochondrial dysfunction. Methods: A 35-year-old woman was ascertained to have ANSD. Exome sequencing identified the genetic cause of hearing loss, and functional study measuring mitochondrial activity was performed to provide molecular evidence of pathophysiology. Expression of FDXR in the mouse cochlea was evaluated by immunohistochemistry. Intraoperatively, electrically-evoked compound action potential (ECAP) responses were measured, and mapping parameters were adjusted accordingly. Audiological outcomes were monitored for over 1 year. Results: In lymphoblastoid cell lines (LCLs) carrying a novel FDXR variant, decreased ATP and MtMP levels and increased ROS levels were observed compared to control LCLs. These dysfunctions were restored by administering mitochondria isolated from umbilical cord mesenchymal stem cells, confirming the pathogenic potential of this variant via mitochondrial dysfunction. Partial ECAP responses during CI and FDXR expression in the mouse cochlea indicate that FDXR-related ANSD is postsynaptic. By increasing the pulse width during mapping, the patient's CI outcomes showed significant improvement over 1-year post-CI. Conclusion: Post-synaptic ANSD due to a novel FDXR variant linked to mitochondrial dysfunction was identified first in a Korean, and 1-year post CI outcomes were reported for the first time in the literature. Excellent audiologic results were obtained, and our results reiterate the correlation between genotype and CI outcomes in ANSD.
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BACKGROUND: The autonomic nervous system plays an important role in atrial fibrillation (AF) and hypertension. Renal denervation (RDN) lowers blood pressure (BP), but its role in AF is poorly understood. OBJECTIVES: The purpose of this study was to investigate whether RDN reduces AF recurrence after pulmonary vein isolation (PVI). METHODS: This study randomized patients from 8 centers (United States, Germany) with drug-refractory AF for treatment with PVI+RDN vs PVI alone. A multielectrode radiofrequency Spyral catheter system was used for RDN. Insertable cardiac monitors were used for continuous rhythm monitoring. The primary efficacy endpoint was ≥2 minutes of AF recurrence or repeat ablation during all follow-up. The secondary endpoints included atrial arrhythmia (AA) burden, discontinuation of class I/III antiarrhythmic drugs, and BP changes from baseline. RESULTS: A total of 70 patients with AF (52 paroxysmal, 18 persistent) and uncontrolled hypertension were randomized (RDN+PVI, n = 34; PVI, n = 36). At 3.5 years, 26.2% and 21.4% of patients in RDN+PVI and PVI groups, respectively, were free from the primary efficacy endpoint (log rank P = 0.73). Patients with mean ≥1 h/d AA had less daily AA burden after RDN+PVI vs PVI (4.1 hours vs 9.2 hours; P = 0.016). More patients discontinued class I/III antiarrhythmic drugs after RDN+PVI vs PVI (45% vs 14%; P = 0.040). At 1 year, systolic BP changed by -17.8 ± 12.8 mm Hg and -13.7 ± 18.8 mm Hg after RDN+PVI and PVI, respectively (P = 0.43). The composite safety endpoint was not significantly different between groups. CONCLUSIONS: In patients with AF and uncontrolled BP, RDN+PVI did not prevent AF recurrence more than PVI alone. However, RDN+PVI may reduce AF burden and antiarrhythmic drug usage, but this needs further prospective validation.
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Purpose: When healthcare professionals use biased or stigmatizing language to describe people or conditions, it can impact the quality of care or erode the patient-physician relationship. It is not clear where healthcare professionals acquire biased and stigmatizing language in practice. This study focuses on examining language in educational materials used in training of medical students. Specifically, medical biochemistry textbooks were examined as they are often a first exposure to clinical narratives and communication standards. The aim of this project is to investigate whether medical biochemistry textbooks, widely recommended in preclinical UME, model inclusive language communication in clinical narratives. Methods: To determine if educational materials follow inclusive writing guidelines, we conducted a modified document analysis on a sample of medical biochemistry textbooks when clinical scenarios were described. Three independent researchers separately reviewed the textbooks, coded the language using NVivo, and generated themes. Results: Our results show that medical biochemistry textbooks contain language which is not in alignment with the best practices for inclusive language. Our analysis mapped codes to two primary themes of language misalignment. The first theme, "clinical language" (n = 92), included the following codes: difficult patient, general negative descriptive language, patient as failure, and questioning patient credibility. The second primary theme, "identity-first labeling" (n = 251), included 21 codes. Conclusion: This study provides early evidence that the language used in medical biochemistry textbooks to describe people and conditions is not in alignment with inclusive language recommendations. This can reinforce the way future healthcare professionals speak to and about their patients.
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PURPOSE: This study aimed to determine the impact of an intervention using voice recording of family members on pain, anxiety, and agitation in patients undergoing weaning from mechanical ventilation. METHODS: A randomized control pre-post experimental design was implemented to 53 participants, with 27 and 26 participants in the experimental and control groups, respectively. A 70-second voice recording of a family member, repeated three times at 10-minute intervals was used as an intervention for the experimental group. Meanwhile, participants in the control group used headset for 30 minutes. Structured instruments were utilized to measure pain, anxiety, agitation, and the weaning process. Wilcoxon Signed Ranks test and the Mann-Whitney U test, or χ² test, were used for data analysis. RESULTS: The experimental group exhibited significant decrease in pain (Z = -3.53, p < .001), anxiety (t = 5.45, p < .001), and agitation (Z = -2.99, p = .003) scores compared with those of the control group. However, there was no significant difference between groups in the weaning process' simplification (χ² = 0.63, p = .727). CONCLUSION: Intervention using family members' voice recording effectively reduces pain, anxiety, and agitation in patients undergoing weaning from mechanical ventilation. This can be actively utilized to provide a more comfortable process for patients.
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Respiração Artificial , Desmame do Respirador , Humanos , Ansiedade , Família , DorRESUMO
Objective: This study aimed to assess the treatment compliance, patterns, healthcare resource utilization (HCRU), and costs of anti-epilepsy drugs (AEDs) as the first add-on therapy in patients with epilepsy. Methods: We conducted a retrospective population-based cohort study using Korean National Health Insurance claims data from 2016 to 2020. Patients with epilepsy who newly received AED add-on therapy were identified and followed for up to 12 months to evaluate persistence, adherence, treatment patterns, HCRU, and costs. Results: Among 6,746 patients who initiated AED add-on therapy, 65.5% were persistent on their index AED add-on from the index date until the end of the follow-up period, and the mean persistent time on the index add-on was 307.3 ± 92.3 days. A total of 76.8% patients were adherent, with a medication possession ratio (MPR) ≥80%, and the mean MPR was 88.9 ± 25.4%. Persistence and adherence to the index AED add-on were relatively higher among patients prescribed lamotrigine, levetiracetam, oxcarbazepine, and perampanel than those prescribed carbamazepine, topiramate, or valproate. A total of 41.0% of the patients changed their index AED add-on during the follow-up period. The carbamazepine, topiramate, and valproate groups had higher rates of change than the other AED groups. HCRU and costs tended to be lower in the lamotrigine, levetiracetam, oxcarbazepine, and perampanel groups. Furthermore, perampanel showed the lowest HCRU and costs for all-cause cases as well as the lowest length of stay and outpatient visits for epilepsy-related cases. Conclusion: In this population-based study, the use of lamotrigine, levetiracetam, oxcarbazepine, or perampanel as the first add-on therapy in patients with epilepsy contributed to better treatment compliance and lower HCRU and costs than that of carbamazepine, topiramate, or valproate.
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OBJECTIVES: The recent expansion of eligibility for cochlear implantation (CI) by the U.S. Food and Drug Administration (FDA) to include infants as young as 9 months has reignited debates concerning the clinically appropriate cut-off age for pediatric CI. Our study compared the early postoperative trajectories of receptive and expressive language development in children who received CI before 9 months of age with those who received it between 9 and 12 months. This study involved a unique pediatric cohort with documented etiology, where the timing of CI was based on objective criteria and efforts were made to minimize the influence of parental socioeconomic status. METHODS: A retrospective review of 98 pediatric implantees recruited at a tertiary referral center was conducted. The timing of CI was based on auditory and language criteria focused on the extent of delay corresponding to the bottom 1st percentile of language development among age-matched controls, with patients categorized into very early (CI at <9 months), early (CI at 9-12 months) and delayed (CI at 12-18 months) CI groups. Postoperative receptive/expressive language development was assessed using the Sequenced Language Scale for Infants receptive and expressive standardized scores and percentiles. RESULTS: Only the very early CI group showed significant improvements in receptive language starting at 3 months post-CI, aligning with normal-hearing peers by 9 months and maintaining this level until age 2 years. During this period (<2 years), all improvements were more pronounced in receptive language than in expressive language. CONCLUSION: CI before 9 months of age significantly improved receptive language development compared to later CI, with improvements sustained at least up to the age of 2. This study supports the consideration of earlier CI, beyond pediatric Food and Drug Administration labeling criteria (>9 months), in children with profound deafness who have a clear deafness etiology and language development delays (<1st percentile).
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Vaccinating young children against rotavirus (RV) is a promising preventive strategy against rotavirus gastroenteritis (RVGE). We evaluated the relative risk reduction of RVGE induced by universal vaccination in Vietnam through dynamic model analysis. We developed an age-stratified dynamic Vaccinated-Susceptible-Infectious-Recovered-Susceptible model to analyze RV transmission and assess vaccine effectiveness (VE). We assumed 3 different vaccine efficacies: 55%, 70%, and 85%. For model calibration, we used a database of patients under 5 years of age admitted to Ho Chi Minh No.1 Hospital with RVGE between January 2013 and December 2018. Assuming a vaccination rate of 95%, the number of RVGE hospitalizations after 5 years from universal RV vaccination decreased from 92,502 cases to 45,626 with 85% efficacy, to 54,576 cases with 70% efficacy, and to 63,209 cases with 55% efficacy. Additionally, RVGE hospitalizations after 10 years decreased from 177,950 to 89,517 with 85% efficacy and to 121,832 cases with 55% efficacy. The relative risk reductions of RVGE after 10 years were 49.7% with 85% efficacy, 40.6% with 70% efficacy, and 31.5% with 55% efficacy. The VE was 1.10 times (95% CI, 1.01-1.22) higher in the 4-months to 1-year-old age group than in the other age groups (P = 0.038), when applying 85% efficacy with 95% coverage. In conclusion, despite its relatively lower efficacy compared to high-income countries, RV vaccination remains an effective intervention in Southwestern Vietnam. In particular, implementing universal RV vaccination with higher coverage would result in a decrease in RVGE hospitalizations among Vietnamese children under 5 years of age.
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Gastroenterite , Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Criança , Humanos , Lactente , Pré-Escolar , Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Vietnã/epidemiologia , Vacinas contra Rotavirus/uso terapêutico , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Vacinação , Hospitalização , Modelos TeóricosRESUMO
BACKGROUND: The present study aimed to evaluate the long-term oncological and obstetric outcomes following the loop electrosurgical excision procedure (LEEP) in patients with cervical intraepithelial neoplasia (CIN) and investigate the risk factors for recurrence and preterm birth. METHODS: This retrospective cohort study included patients who underwent LEEP for CIN 2-3 between 2011 and 2019. Demographic information, histopathological findings, postoperative cytology, and human papillomavirus (HPV) status were collected and analyzed. The Cox proportional hazards model and Kaplan-Meier curves with the log-rank test were used for risk factor analysis. RESULTS: A total of 385 patients treated with the LEEP were analyzed. Treatment failure, including recurrence or residual disease following surgery, was observed in 13.5% of the patients. Positive surgical margins and postoperative HPV detection were independent risk factors for CIN1 + recurrence or residual disease (HR 1.948 [95%CI 1.020-3.720], p = 0.043, and HR 6.848 [95%CI 3.652-12.840], p-value < 0.001, respectively). Thirty-one patients subsequently delivered after LEEP, and the duration between LEEP and delivery was significantly associated with preterm-related complications, such as a short cervix, preterm labor, and preterm premature rupture of the membrane (p = 0.009). However, only a history of preterm birth was associated with preterm delivery. CONCLUSIONS: Positive HPV status after LEEP and margin status were identified as independent risk factors for treatment failure in patients with CIN who underwent LEEP. However, combining these two factors did not improve the prediction accuracy for recurrence.
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Infecções por Papillomavirus , Nascimento Prematuro , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Gravidez , Feminino , Recém-Nascido , Humanos , Estudos Retrospectivos , Margens de Excisão , Papillomavirus Humano , Eletrocirurgia/métodos , Infecções por Papillomavirus/complicações , Nascimento Prematuro/epidemiologia , Displasia do Colo do Útero/patologia , Recidiva Local de Neoplasia/cirurgiaRESUMO
BACKGROUND: Transplant recipients are immunocompromised and vulnerable to developing tuberculosis. However, active tuberculosis incidence is rapidly declining in South Korea, but the trend of tuberculosis infection among transplant recipients has not been elucidated. This study aimed to evaluate the risk of active tuberculosis after transplantation, including risk factors for tuberculosis and standardized incidence ratios, compared with that in the general population. METHODS: This retrospective study was conducted based on the South Korean health insurance review and assessment database among those who underwent transplantation (62,484 recipients) between 2008 and 2020. Tuberculosis incidence was compared in recipients treated during higher- (2010-2012) and lower-disease burden (2016-2018) periods. Standardized incidence ratios were analyzed using the Korean Tuberculosis Surveillance System. The primary outcome was the number of new tuberculosis cases after transplantation. RESULTS: Of 57,103 recipients analyzed, the overall cumulative incidence rate 1 year after transplantation was 0.8% (95% confidence interval [CI]: 0.7-0.8), significantly higher in the higher-burden period than in the lower-burden period (1.7% vs. 1.0% 3 years after transplantation, P < 0.001). Individuals who underwent allogeneic hematopoietic stem cell transplantation had the highest tuberculosis incidence, followed by those who underwent solid organ transplantation and autologous hematopoietic stem cell transplantation (P < 0.001). The overall standardized incidence ratio was 3.9 (95% CI 3.7-4.2) and was the highest in children aged 0-19 years, at 9.0 (95% CI 5.7-13.5). Male sex, older age, tuberculosis history, liver transplantation, and allogeneic hematopoietic stem cell transplantation were risk factors for tuberculosis. CONCLUSIONS: Transplant recipients are vulnerable to developing tuberculosis, possibly influenced by their immunocompromised status, solid organ transplant type, age, and community prevalence of tuberculosis. Tuberculosis prevalence by country, transplant type, and age should be considered to establish an appropriate tuberculosis prevention strategy for high-risk groups.
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Transplante de Células-Tronco Hematopoéticas , Transplante de Órgãos , Tuberculose , Criança , Humanos , Masculino , Tuberculose/epidemiologia , Estudos Retrospectivos , Transplante de Órgãos/efeitos adversos , Fatores de Risco , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , IncidênciaRESUMO
Peanut (Arachis hypogaea L.) is a globally cultivated crop of significant economic and nutritional importance. The role of gibberellic-acid-stimulated Arabidopsis (GASA) family genes is well established in plant growth, development, and biotic and abiotic stress responses. However, there is a gap in understanding the function of GASA proteins in cultivated peanuts, particularly in response to abiotic stresses such as drought and salinity. Thus, we conducted comprehensive in silico analyses to identify and verify the existence of 40 GASA genes (termed AhGASA) in cultivated peanuts. Subsequently, we conducted biological experiments and performed expression analyses of selected AhGASA genes to elucidate their potential regulatory roles in response to drought and salinity. Phylogenetic analysis revealed that AhGASA genes could be categorized into four distinct subfamilies. Under normal growth conditions, selected AhGASA genes exhibited varying expressions in young peanut seedling leaves, stems, and roots tissues. Notably, our findings indicate that certain AhGASA genes were downregulated under drought stress but upregulated under salt stress. These results suggest that specific AhGASA genes are involved in the regulation of salt or drought stress. Further functional characterization of the upregulated genes under both drought and salt stress will be essential to confirm their regulatory roles in this context. Overall, our findings provide compelling evidence of the involvement of AhGASA genes in the mechanisms of stress tolerance in cultivated peanuts. This study enhances our understanding of the functions of AhGASA genes in response to abiotic stress and lays the groundwork for future investigations into the molecular characterization of AhGASA genes.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arachis/metabolismo , Filogenia , Proteínas de Arabidopsis/genética , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismoRESUMO
BACKGROUND: This 1-year open-label extension study aimed to identify the persistent synergistic effects of allogeneic umbilical cord blood (UCB) cells and erythropoietin (EPO) in children with cerebral palsy (CP) for up to 2 years. METHODS: This open-label extension study followed children with CP who were enrolled in the previous randomized, double blind, placebo-controlled trial. The following groups from the first trial were maintained: (A) UCB + EPO, (B) UCB, (C) EPO, and (D) only placebo, and all the participants had continued active rehabilitation. This extended study started 3 months after termination of the first trial, which had a 1-year follow-up duration. All subjects received single additional UCB intravenous infusion at the extension baseline regardless of their initial allocation. Outcome measures were the gross motor performance measure (GMPM), gross motor function measure-66 (GMFM-66), and Bayley scales of infant development-II (BSID-II), which were followed at 3, 6, and 12 months after the extension baseline. Changes in the outcome scores from the baseline values of the previous trial and this study were analysed. RESULTS: Sixty-nine children (4.29 ± 1.28 years, M:F = 34:35) were included in this study. Each group showed improvements in the outcome measures at 12 months after additional UCB infusion compared to the baseline scores, except for GMFM and GMPM in Group C which were elevated at 3 and 6 months post-therapy. Total subject analyses did not show significant differences in the outcome measures between the four different groups at 3, 6 and 12 months after additional UCB therapy. However, patients with severe dysfunction, whose GMFCS levels were IV and V, revealed a larger improvement of the GMPM score in Group A than in Group D (Ps < 0.05) from the baseline value of the previous trial. The changes in BSID-II mental scale scores were positively correlated with the number of administered total nucleated cells per unit body weight during this one-year extension study period (r = 0.536, P = 0.001). CONCLUSIONS: These results suggest that when administering UCB to treat patients with CP, combination therapy with EPO is more effective, and the effect might last as long as 2 years, especially in patients with severe impairments. TRIAL REGISTRATION: CHA Bundang Medical Center IRB, No. 2015-06-093, approved on July 29, 2015, ( https://www.e-irb.com:3443/devlpg/nlpgS200.jsp ), ClinicalTrials.gov, NCT03130816, retrospectively registered on April 27, 2017 ( https://clinicaltrials.gov/ct2/show/NCT03130816?term=NCT03130816&draw=2&rank=1 ).
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Paralisia Cerebral , Eritropoetina , Criança , Lactente , Humanos , Paralisia Cerebral/tratamento farmacológico , Sangue Fetal , Eritropoetina/uso terapêutico , Células Sanguíneas , Terapia Combinada , Resultado do TratamentoRESUMO
Trampolines are recognized as a valuable tool in exercise and rehabilitation due to their unique properties like elasticity, rebound force, low-impact exercise, and enhancement of posture, balance, and cardiopulmonary function. To quantitatively assess the effects of trampoline exercises, it is essential to estimate factors such as stiffness, elements influencing jump dynamics, and user safety. Previous studies assessing trampoline characteristics had limitations in performing repetitive experiments at various locations on the trampoline. Therefore, this research introduces a robotic system equipped with foot-shaped jigs to evaluate trampoline stiffness and quantitatively measure exercise effects. This system, through automated, repetitive movements at various locations on the trampoline, accurately measures the elastic coefficient and vertical forces. The robot maneuvers based on the coordinates of the trampoline, as determined by its torque and position sensors. The force sensor measures data related to the force exerted, along with the vertical force data at X, Y, and Z coordinates. The model's accuracy was evaluated using linear regression based on Hooke's Law, with Mean Absolute Error (MAE), Root Mean Square Error (RMSE), and Correlation Coefficient Squared (R-squared) metrics. In the analysis including only the distance between X and the foot-shaped jigs, the average MAE, RMSE, and R-squared values were 17.9702, 21.7226, and 0.9840, respectively. Notably, expanding the model to include distances in X, Y, and between the foot-shaped jigs resulted in a decrease in MAE to 15.7347, RMSE to 18.8226, and an increase in R-squared to 0.9854. The integrated model, including distances in X, Y, and between the foot-shaped jigs, showed improved predictive capability with lower MAE and RMSE and higher R-squared, indicating its effectiveness in more accurately predicting trampoline dynamics, vital in fitness and rehabilitation fields.
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Procedimentos Cirúrgicos Robóticos , Extremidade Inferior , Exercício Físico , Pé , Modelos LinearesRESUMO
Purpose: The aim of this study was to compare short-term results from use of the direct anterior approach (DAA) and the conventional posterolateral approach (PLA) in performance of bipolar hemiarthroplasty for treatment of femoral intertrochanteric fractures in elderly patients. Materials and Methods: A retrospective review of 100 patients with intertrochanteric fractures who underwent bipolar hemiarthroplasty was conducted. The PLA was used in 50 cases from 2016 to 2019; since that time we have used the DAA in 50 cases from 2019 to 2021. Measurements of mean operative time, blood loss, hospitalization period, and ambulation status, greater trochanter (GT) migration and stem subsidence were performed. And the incidence of complications was examined. Results: Operative time was 73.60±14.56 minutes in the PLA group and 79.80±8.89 minutes in the DAA group (P<0.05). However, after experiencing 20 cases using DAA, there was no statistically difference in operative time between two groups (P=0.331). Blood loss was 380.76±180.67 mL in the PLA group and 318.14±138.51 mL in the DAA group (P<0.05). The hospitalization was 23.76±11.89 days in the PLA group and 21.45±4.18 days in the DAA group (P=0.207). In both groups, there were no progressive GT migration, intraoperative fractures or dislocations, although there was one case of infection in the PLA group. Conclusion: Although use of the DAA in performance of bipolar hemiarthroplasty required slightly more time in the beginning compared with the PLA, the DAA may well be an alternative, safe surgical technique as a muscle preserving procedure in elderly patients with intertrochanteric fractures.
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Purpose: To figure out how complete control of family visits to prevent infection of coronavirus disease 2019 (COVID-19) affected the activity recovery of hip fracture patients admitted to nursing hospitals. Materials and Methods: Eighty-one patients with hip surgery in the two years prior to COVID-19 pandemic were classified as Group A, and 103 patients in the next two years were designated as Group B. The subjects' walking ability was evaluated by using the modified Koval index (MKI). In order to analyze the impact of the family visit control to the subjects, each group was classified into two different groups: (1) inpatients group who admitted to nursing hospitals and (2) home-treated patients. Additionally, statistical elements were processed in consideration of other factors that may affect the results of the experiment. Results: The MKI evaluated at 6 months postoperative was 3.31±1.79 in Group A and 2.77±1.91 in Group B, and it was meaningfully low after the pandemic (P=0.04). There was significantly low among both of Group A 2.74±1.76 and Group B 1.93±1.81 after the pandemic (P=0.03) among those treated at the nursing hospital. The rate of deterioration of the MKI was 35 (43.2%) in Group A and 57 (55.3%) in Group B, which increased by 12.1% after the pandemic. Conclusion: The pandemic had a negative effect on the recovery of postoperative activities of elderly hip fracture patients who admitted to nursing hospitals when family access was completely restricted to prevent infection.
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Sesame (Sesamum indicum L.), an oilseed crop, is gaining worldwide recognition for its healthy functional ingredients as consumption increases. The content of lignans, known for their antioxidant and anti-inflammatory effects, is a key agronomic trait that determines the industrialization of sesame. However, the study of the genetics and physiology of lignans in sesame is challenging, as they are influenced by multiple genes and environmental factors, therefore, the understanding of gene function and synthetic pathways related to lignan in sesame is still limited. To address these knowledge gaps, we conducted genetic analyses using F7 recombinant inbred line (RIL) populations derived from Goenbaek and Gomazou as low and high lignin content variants, respectively. Using the QTL-seq approach, we identified three loci, qLignan1-1, qLignan6-1, and qLignan11-1, that control lignan content, specifically sesamin and sesamolin. The allelic effect between loci was evaluated using the RIL population. qLignan6-1 had an additive effect that increased lignan content when combined with the other two loci, suggesting that it could be an important factor in gene pyramiding for the development of high-lignan varieties. This study not only highlights the value of sesame lignan, but also provides valuable insights for the development of high-lignan varieties through the use of DNA markers in breeding strategies. Overall, this research contributes to our understanding of the importance of sesame oil and facilitates progress in sesame breeding for improved lignan content.
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Emotion regulation is important for psychological health and can be achieved by implementing various strategies. How one regulates emotions is critical for maximizing psychological health. Few studies, however, tested the psychological correlates of different emotion regulation strategies across multiple cultures. In a preregistered cross-cultural study (N = 3,960, 19 countries), conducted during the COVID-19 pandemic, we assessed associations between the use of seven emotion regulation strategies (situation selection, distraction, rumination, cognitive reappraisal, acceptance, expressive suppression, and emotional support seeking) and four indices of psychological health (life satisfaction, depressive symptoms, perceived stress, and loneliness). Model comparisons based on Bayesian information criteria provided support for cultural differences in 36% of associations, with very strong support for differences in 18% of associations. Strategies that were linked to worse psychological health in individualist countries (e.g., rumination, expressive suppression) were unrelated or linked to better psychological health in collectivist countries. Cultural differences in associations with psychological health were most prominent for expressive suppression and rumination and also found for distraction and acceptance. In addition, we found evidence for cultural similarities in 46% of associations between strategies and psychological health, but none of this evidence was very strong. Cultural similarities were most prominent in associations of psychological health with emotional support seeking. These findings highlight the importance of considering the cultural context to understand how individuals from diverse backgrounds manage unpleasant emotions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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OBJECTIVE: This study aimed to investigate the feasibility of ultrafast magnetic resonance imaging (MRI) and radiomic features derived from breast MRI for predicting the upstaging of ductal carcinoma in situ (DCIS) diagnosed using percutaneous needle biopsy. MATERIALS AND METHODS: Between August 2018 and June 2020, 95 patients with 98 DCIS lesions who underwent preoperative breast MRI, including an ultrafast sequence, and subsequent surgery were included. Four ultrafast MRI parameters were analyzed: time-to-enhancement, maximum slope (MS), area under the curve for 60 s after enhancement, and time-to-peak enhancement. One hundred and seven radiomic features were extracted for the whole tumor on the first post-contrast T1WI and T2WI using PyRadiomics. Clinicopathological characteristics, ultrafast MRI findings, and radiomic features were compared between the pure DCIS and DCIS with invasion groups. Prediction models, incorporating clinicopathological, ultrafast MRI, and radiomic features, were developed. Receiver operating characteristic curve analysis and area under the curve (AUC) were used to evaluate model performance in distinguishing between the two groups using leave-one-out cross-validation. RESULTS: Thirty-six of the 98 lesions (36.7%) were confirmed to have invasive components after surgery. Compared to the pure DCIS group, the DCIS with invasion group had a higher nuclear grade (P < 0.001), larger mean lesion size (P = 0.038), larger mean MS (P = 0.002), and different radiomic-related characteristics, including a more extensive tumor volume; higher maximum gray-level intensity; coarser, more complex, and heterogeneous texture; and a greater concentration of high gray-level intensity. No significant differences in AUCs were found between the model incorporating nuclear grade and lesion size (0.687) and the models integrating additional ultrafast MRI and radiomic features (0.680-0.732). CONCLUSION: High nuclear grade, larger lesion size, larger MS, and multiple radiomic features were associated with DCIS upstaging. However, the addition of MS and radiomic features to the prediction model did not significantly improve the prediction performance.
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Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Imageamento por Ressonância Magnética/métodos , Biópsia por Agulha , Curva ROC , Neoplasias da Mama/diagnóstico por imagem , Estudos RetrospectivosRESUMO
GNE myopathy, caused by biallelic mutations in the GNE gene, is characterized by initial ankle dorsiflexor weakness and rimmed vacuoles in the muscle histopathology, resulting in reduced sialic acid production. Sialyllactose is a source of sialic acid. We performed a pilot clinical trial to analyze the pharmacokinetic properties of 6'-sialyllactose (6SL) and evaluated the safety, and efficacy of oral 6SL in patients with GNE myopathy. Ten participants were in the pharmacokinetic study, and 20 in the subsequent clinical trial. For the pharmacokinetic study, participants were administered either 3 g (low-dose) or 6 g (high-dose) of 6SL in a single dose. Plasma concentrations of 6SL, sialic acid, and sialic acid levels on the surface of red blood cells were periodically assessed in blood samples. Patients were randomly allocated to test (low- and high-dose groups) or placebo groups for the trial. Motor function, ambulation, plasma 6SL and sialic acid concentrations, GNE myopathy-functional activity scale scores, and MRI findings were assessed. 6SL was well tolerated, except for self-limited gastrointestinal discomfort. Free sialic acid in both low- and high-dose groups significantly increased at 6 and 12 weeks, but not in the placebo group. In the high-dose group, proximal limb powers improved with daily 6SL. Considering the fat fraction on muscle MRI, results in the high-dose group were superior to those in the low-dose group. 6SL may be a good candidate for GNE myopathy therapeutics as it induces an increase or reduces the decrease in limb muscle power, attenuates muscle degeneration, and improves the biochemical properties of sialic acid.
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Miopatias Distais , Ácido N-Acetilneuramínico , Humanos , Ácido N-Acetilneuramínico/uso terapêutico , Projetos Piloto , Miopatias Distais/tratamento farmacológico , Miopatias Distais/genética , Miopatias Distais/patologia , Resultado do Tratamento , Músculo Esquelético/patologia , MutaçãoRESUMO
Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof-of-principle evidence is presented that a cell-penetrable peptide (ACP52C) dissociates transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene-addicted cancer cells through transcription activity-independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2-p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome-wide DNA strand breaks and subsequent catastrophic DNA damage responses. These two mechanisms are independent of cancer driver mutations but are hindered by high MDM2 p60 expression. However, resistance to ACP52C mediated by MDM2 p60 can be sensitized by CASP2 inhibition. Additionally, derivatives of ACP52C conjugated with fatty acid alone or with a CASP2 inhibiting peptide show improved pharmacokinetics and reduced cancer burden, even in ACP52C-resistant cancers. This study enhances the understanding of ACP52C-induced cancer-specific apoptosis induction and supports the use of ACP52C in anticancer drug development.