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Osteoarthritis (OA) is a chronic disease affecting joints and further causing disabilities. This disease affects around 240 million people worldwide. It is a multifactorial disease, and its etiology is difficult to determine. Although numerous therapeutic strategies are available, the therapies are aimed at reducing pain and improving patients' quality of life. Hence, there is an urgent need to develop disease-modifying drugs (DMOAD) that can reverse or halt OA progression. Apoptosis is a cell removal process that is important in maintaining homeostatic mechanisms in the development and sustaining cell population. The apoptosis of chondrocytes is believed to play an important role in OA progression due to poor chondrocytes self-repair abilities to maintain the extracellular matrix (ECM). Hence, targeting chondrocyte apoptosis can be one of the potential therapeutic strategies in OA management. There are various mediators and targets available to inhibit apoptosis such as autophagy, endoplasmic reticulum (ER) stress, oxidative stress, and inflammation. As such, this review highlights the importance and potential targets that can be aimed to reduce chondrocyte apoptosis.
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BACKGROUND: Recent findings suggest a link between gout and the development of dementia. Early treatment with colchicine is recommended as a first-line therapy for gout flares. Animal studies demonstrate that colchicine could induce cognitive impairment. This cohort study aimed to investigate the association between colchicine use and the risk of developing dementia. METHODS: In this nationwide cohort study, we performed comparative analysis on 6147 patients ≥40 years, with gout and colchicine new users against 6147 controls to assess subsequent dementia risk. The colchicine group and the control group (urate lowering therapy group) were matched on the bases of age, sex, index year, and comorbidities. All participants were followed for up to 14 years for a diagnosis of dementia considering medical records were retrospectively checked over this period. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Sensitivity analyses were performed to validate our findings. RESULTS: The adjusted hazard ratio (aHR) of dementia for colchicine users was 1.45 (95% CI = 1.05, 1.99) relative to comparison group after adjusting for sex, age, and comorbidities. Sensitivity analysis aiming to minimize underdiagnosed occult dementia at the time of index year yielded consistent positive association. In higher accumulative dose colchicine group (cumulative defined daily dose [cDDD] >30), the aHR of dementia risk for colchicine users was 1.42 (95% CI = 1.03, 1.97) compared with nonusers. For those duration of colchicine use >30 days, the aHR was 1.53 (95% CI = 1.01-2.32) compared to the nonuser group. CONCLUSIONS: A significant risk of dementia was observed in this study in patients with gout using colchicine at higher cDDD and for a longer period. Further research is needed to elucidate the relationship between colchicine, gout, and dementia.
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Colchicina , Demencia , Supresores de la Gota , Gota , Humanos , Colchicina/efectos adversos , Colchicina/uso terapéutico , Gota/epidemiología , Gota/tratamiento farmacológico , Demencia/epidemiología , Demencia/inducido químicamente , Demencia/diagnóstico , Femenino , Masculino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Supresores de la Gota/efectos adversos , Factores de Riesgo , Medición de Riesgo , Factores de Tiempo , Taiwán/epidemiología , Adulto , Anciano de 80 o más Años , Bases de Datos FactualesRESUMEN
Narrowband emissive multiresonant thermally activated delayed fluorescence (MR-TADF) emitters are a promising solution to achieve the current industry-targeted color standard, Rec. BT.2020-2, for blue color without using optical filters, aiming for high-efficiency organic light-emitting diodes (OLEDs). However, their long triplet lifetimes, largely affected by their slow reverse intersystem crossing rates, adversely affect device stability. In this study, a helical MR-TADF emitter (f-DOABNA) is designed and synthesized. Owing to its π-delocalized structure, f-DOABNA possesses a small singlet-triplet gap, ΔEST, and displays simultaneously an exceptionally faster reverse intersystem crossing rate constant, kRISC, of up to 2 × 106 s-1 and a very high photoluminescence quantum yield, ΦPL, of over 90% in both solution and doped films. The OLED with f-DOABNA as the emitter achieved a narrow deep-blue emission at 445 nm (full width at half-maximum of 24 nm) associated with Commission Internationale de l'Éclairage (CIE) coordinates of (0.150, 0.041), and showed a high maximum external quantum efficiency, EQEmax, of ≈20%.
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To fulfill ultra-high-definition display, efficient and bright green organic light-emitting diodes with Commission Internationale de l'Éclairage y-coordinate ≥ 0.7 are required. Although there are some preceding reports of highly efficient devices based on pure-green multi-resonance emitters, the efficiency rolloff and device stabilities for those pure-green devices are still unsatisfactory. Herein, we report the rational design of two pure-green multi-resonance emitters for achieving highly stable and efficient pure-green devices with CIEx,ys that are close to the NTSC and BT. 2020 standards. In this study, our thermally activated delayed fluorescence OLEDs based on two pure-green multi-resonance emitters result in CIEy up to 0.74. In hyperfluorescent device architecture, the CIExs further meet the x-coordinate requirements, i.e., NTSC (0.21) and BT. 2020 (0.17), while keeping their CIEys ~ 0.7. Most importantly, hyperfluorescent devices display the high maximum external quantum efficiencies of over 25% and maximum luminance of over 105 cd m-2 with suppressed rolloffs (external quantum efficiency of ~20% at 104 cd m-2) and long device stabilities with LT95s of ~ 600 h.
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Introduction: The Allocation System for changes in Equity in Kidney Transplantation (ASCENT) study was a hybrid type 1 trial of a multicomponent intervention among 655 US dialysis facilities with low kidney transplant waitlisting to educate staff and patients about kidney allocation system (KAS) changes and increase access to and reduce racial disparities in waitlisting. Intervention components included a staff webinar, patient and staff educational videos, and facility-specific feedback reports. Methods: Implementation outcomes were assessed using the Reach, Effectiveness, Adoption, Implementation, and Maintenance Framework. Postimplementation surveys were administered among intervention group facilities (n = 334); interviews were conducted with facility staff (n = 6). High implementation was defined as using 3 to 4 intervention components, low implementation as using 1 to 2 components, and nonimplementation as using no components. Results: A total of 331 (99%) facilities completed the survey; 57% were high implementers, 31% were low implementers, and 12% were nonimplementers. Waitlisting events were higher or similar among high versus low implementer facilities for incident and prevalent populations; for Black incident patients, the mean proportion waitlisted in low implementer facilities was 0.80% (95% confidence interval [CI]: 0.73-0.87) at baseline and 0.55% at 1-year (95% CI: 0.48-0.62) versus 0.83% (95% CI: 0.78-0.88) at baseline and 1.40% at 1-year (95% CI: 1.35-1.45) in high implementer facilities. Interviews revealed that the intervention helped facilities prioritize transplant education, but that intervention components were not uniformly shared. Conclusion: The findings provide important context to interpret ASCENT effectiveness results and identified key barriers and facilitators to consider for future modification and scale-up of multilevel, multicomponent interventions in dialysis settings.
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The investigation of organic light-emitting diodes (OLEDs) and organic laser devices with thermally activated delayed fluorescence (TADF) molecules is emerging due to the potential of harnessing triplets. In this work, a boron/nitrogen multiple-resonance TADF polycyclic framework fusing carbazole units (CzBNPh) was proposed. CzBNPh exhibited a narrowband emission (<30â nm), a unity photoluminescence quantum yield, and a fast radiative rate. Consequently, CzBNPh demonstrated a low distributed feedback (DFB) lasing threshold of 0.68â µJ cm-2 . Furthermore, the stimulated emission zone of CzBNPh was effectively separated from its singlet and triplet absorption, thereby minimizing the singlet-triplet annihilation under long-pulsed excitation ranging from 20â µs to 2.5â ms. Significantly, the enhanced rigid molecular conformation, thermal stability, and photo-stability resulted in improved lasing and electroluminescence stability compared to that of 5,9-diphenyl-5,9-diaza-13b-boranaphtho[3,2,1-de]anthracene (DABNA)-core. These findings indicate the potential of CzBN-core as a promising framework for achieving long-pulsed wave and electrically-pumped lasing in the future.
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Enfermedades Autoinmunes , Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Estudios de Cohortes , Taiwán/epidemiología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/epidemiología , Relaciones Madre-HijoAsunto(s)
Glaucoma , Lupus Eritematoso Sistémico , Humanos , Estudios de Cohortes , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Factores de Riesgo , Glaucoma/diagnóstico , Glaucoma/epidemiología , Glaucoma/etiologíaRESUMEN
Human platelet lysate (hPL) has high levels of fibrinogen and coagulation factors, which can lead to gel and precipitate formation during storage and cell culture. Heparin derived from animals is commonly added to minimize these risks, but cannot completely eliminate them. Thus, this study proposes an alternative method to prepare fibrinogen-depleted hPL (Fd-hPL) that supports heparin-free expansion of mesenchymal stem cells (MSCs). hPL was added to heparin to prepare heparin-hPL (H-hPL), whilst Fd-hPL was prepared by adding calcium salt to hPL to remove the fibrin clot. The concentrations of calcium, fibrinogen, and growth factors in H-hPL and Fd-hPL were compared. The effects of H-hPL and Fd-hPL on umbilical cord-derived MSCs (UC-MSCs) were assessed. The results showed that Fd-hPL possessed a significantly higher calcium concentration and a lower fibrinogen level than H-hPL. The concentrations of BDNF, TGF-ß1, and PDGF-BB showed no significant difference between H-hPL and Fd-hPL, but Fd-hPL had a lower VEGF concentration. Fd-hPL retained the characteristics of UC-MSCs, as it did not affect the cell viability, proliferation, multilineage differentiation potential, or surface marker expression. In conclusion, Fd-hPL effectively supported the in vitro expansion of MSCs without compromising their characteristics, positioning it as a potential substitute for FBS in MSC culture.
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OBJECTIVE: To examine the impact of nutritional and physical activity (PA) policies and practices at early care and education centres on behavioural changes among children ages 2-5. METHODS: The study population included 586 children from 25 education centres throughout the state of Georgia. Policies and practices were measured using the Georgia Nutrition and PA Assessment at the start of school year in Fall 2017. Survey data were collected at the beginning of school year September/October 2017 and at the end of school year April/May 2018 to measure changes in children's nutritional and PA behaviour over the school year. We used generalised estimating equations to estimate odds ratios and 95% confidence intervals. RESULTS: Children at centres with a high nutrition assessment score had higher odds of increasing vegetable consumption (OR = 2.1; 95% CI: 1.1, 4.0) while the odds of increasing fruit (OR = 1.4; 95% CI: 0.8, 2.4) and water (OR = 1.2; 95% CI: 0.5, 2.7) consumption increased non-significantly. The odds of improving PA were similar between children at centres with a high versus a low PA assessment score. CONCLUSION: The results, though insignificant, indicate that policies and practices could influence children's health behaviours. Further research is warranted to examine whether improvements in policies and practices could explain changes in children's health behaviours, the impact of educator's knowledge on children's health behaviours and the implementation of and adherence to policy and practice improvement plans.
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Salud Infantil , Ejercicio Físico , Humanos , Niño , Estado Nutricional , Conductas Relacionadas con la Salud , PolíticasRESUMEN
Introduction: Rehospitalization after kidney transplant is costly to patients and health care systems and is associated with poor outcomes. Few prediction model studies have examined whether inclusion of clinical notes data from the electronic medical record (EMR) enhances prediction of rehospitalization. Methods: In a retrospective, observational study of first-time, adult kidney transplant recipients at a large, urban hospital in southeastern United States (2005-2015), we examined 30-day rehospitalization (30DR) using structured EMR and unstructured (i.e., clinical notes) data. We used natural language processing (NLP) methods on 8 types of clinical notes and included terms in predictive models using unsupervised machine learning approaches. Both the area under the receiver operating curve and precision-recall curve (ROC and PRC, respectively) were used to determine and compare model accuracy, and 5-fold cross-validation tested model performance. Results: Among 2060 kidney transplant recipients, 30.7% were readmitted within 30 days. Predictive models using clinical notes did not meaningfully improve performance over previous models using structured data alone (ROC 0.6821; 95% confidence interval [CI]: 0.6644, 0.6998). Predictive models built using solely clinical notes performed worse than models using both clinical notes and structured data. The data that contributed to the top performing models were not identical but both included structured data and progress notes (ROC 0.6902; 95% CI: 0.6699, 0.7105). Conclusions: Including new features from clinical notes in risk prediction models did not substantially increase predictive accuracy for 30DR for kidney transplant recipients. Future research should consider pooling data from multiple institutions to increase sample size and avoid overfitting models.
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BACKGROUND: The US kidney allocation system (KAS) changed in 2014, but dialysis facility staff (including nephrologists, social workers, nurse managers, and facility administrators) had low awareness of how this policy change could affect their patients' access to transplant. We assessed the effectiveness of a multicomponent and multilevel educational and outreach intervention targeting US dialysis facilities with low waitlisting, with a goal of increasing waitlisting and reducing Black versus White racial disparities in waitlisting. METHODS: The Allocation System Changes for Equity in Kidney Transplantation (ASCENT) study was a cluster-randomized, pragmatic, multilevel, effectiveness-implementation trial including 655 US dialysis facilities with low waitlisting, randomized to receive either the ASCENT intervention (a performance feedback report, a webinar, and staff and patient educational videos) or an educational brochure. Absolute and relative differences in coprimary outcomes (1-year waitlisting and racial differences in waitlisting) were reported among incident and prevalent patients. RESULTS: Among 56,332 prevalent patients, 1-year waitlisting decreased for patients in control facilities (2.72%-2.56%) and remained the same for patients in intervention facilities (2.68%-2.75%). However, the proportion of prevalent Black patients waitlisted in the ASCENT interventions increased from baseline to 1 year (2.52%-2.78%), whereas it remained the same for White patients in the ASCENT intervention facilities (2.66%-2.69%). Among incident patients in ASCENT facilities, 1-year waitlisting increased among Black patients (from 0.87% to 1.07%) but declined among White patients (from 1.54% to 1.27%). Significant racial disparities in waitlisting were observed at baseline, with incident Black patients in ASCENT facilities less likely to waitlist compared with White patients (adjusted odds ratio [aOR], 0.56; 95% confidence interval [CI], 0.35 to 0.92), but 1 year after the intervention, this racial disparity was attenuated (aOR, 0.84; 95% CI, 0.49 to 1.42). CONCLUSIONS: The ASCENT intervention may have a small effect on extending the reach of the new KAS policy by attenuating racial disparities in waitlisting among a population of US dialysis facilities with low waitlisting. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: National Institutes of Health ( NCT02879812 ). PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_03_08_CJN09760822.mp3.
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Fallo Renal Crónico , Trasplante de Riñón , Humanos , Diálisis Renal , Disparidades en Atención de Salud , Riñón , Grupos Raciales , Fallo Renal Crónico/epidemiología , Listas de EsperaRESUMEN
BACKGROUND: Inadequate sleep has been shown to have detrimental effects on academic performance, physical, mental, and emotional health among adolescents. Factors that influence sleep have been identified. However, most literature is currently limited to urban settings. This study sought to identify factors that influence sleep habits among high school students in a semi-rural community. METHODS: Twelve focus groups were conducted in-person with separate groups of students, parents, and school staff in October 2019. Discussions focused on sleep experiences, knowledge, environment, and factors influencing sleep. Data were coded using grounded theory approach. Themes were identified through summative content analysis. RESULTS: Four major themes were identified: (1) inadequate sleep adversely affects academic performance and emotional health; (2) students face a gap in knowledge regarding sleep duration; (3) academic and nonacademic activities compete with sleep needs; and (4) night-time use of technology negatively influences sleep habits. CONCLUSIONS: Our findings suggest that high school students do not get adequate sleep, largely due to the demands of academic and extracurricular activities and the use of electronics at night. These results can guide the development of targeted sleep education and intervention programs.
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Población Rural , Privación de Sueño , Adolescente , Humanos , Georgia , Estudiantes/psicología , SueñoRESUMEN
Multiple-resonance thermally activated delayed fluorescence (MR-TADF) emitters have emerged as an important component of organic light-emitting diodes (OLEDs) because of their narrowband emission and high exciton utilization efficiency. However, the chemical space of MR-TADF emitters remains mostly unexplored because of the lack of suitable synthetic protocols. Herein, we demonstrate a sequential multiple borylation reaction that provides new synthetically accessible chemical space. ω-DABNA, the proof-of-concept material, exhibited narrowband green TADF with a full width at half-maximum of 22 nm and a small singlet-triplet energy gap of 13 meV. The OLED employing it as an emitter exhibited electroluminescence at 512 nm, with Commission International de l'Éclairage coordinates of (0.13, 0.73) and a high external quantum efficiency (EQE) of 31.1%. Moreover, the device showed minimum efficiency roll-off, with an EQE of 29.4% at 1000 cd m-2.
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We studied the photophysical and electroluminescent (EL) characteristics of a series of azaborine derivatives having a pair of boron and nitrogen aimed at the multi-resonance (MR) effect. The computational study with the STEOM-DLPNO-CCSD method clarified that the combination of a BN ring-fusion and a terminal carbazole enhanced the MR effect and spin-orbit coupling matrix element (SOCME), simultaneously. Also, we clarified that the second triplet excited state (T2) plays an important role in efficient MR-based thermally activated delayed fluorescence (TADF). Furthermore, we obtained a blue-violet OLED with an external EL quantum efficiency (EQE) of 9.1%, implying the presence of a pronounced nonradiative decay path from the lowest triplet excited state (T1).
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Osteoarthritis (OA) is the most common type of arthritis and chronic joint disease, affecting more than 240 million people worldwide. Although there are numerous advances in using drugs in treating OA, the use of natural compounds has aroused much interest among researchers due to their safety margin. Recent discovery shows that natural compounds play an extensive role in the oxidative stress signaling pathway in treating OA. Thus, this review summarizes the commonly used natural compounds for treating OA focusing on the oxidative stress signaling pathway and its downstream mediators. Selected databases-such as Scopus, Web of Science, Nature, and PubMed-were used to search for potentially relevant articles. The search is limited to the last 15 years and the search was completed using the Boolean operator's guideline using the keywords of natural product AND oxidative stress AND osteoarthritis OR natural extract AND ROS AND degenerative arthritis OR natural plant AND free radicals AND degenerative joint disease. In total, 37 articles were selected for further review. Different downstream mechanisms of oxidative stress involved in the usage of natural compounds for OA treatment and anabolic and catabolic effects of natural compounds that exhibit chondroprotective effects have been discussed with the evidence of in vitro and in vivo trials in this review.
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A series of poly(butylene adipate-co-hexamethylene adipate) (PBHA) copolymers with different content of 1,4-cyclohexanedimethanol (CHDM) was synthesized via one-step melt polymerization. The PBHA copolymer with 5 mol% CHDM (PBHA-C5) exhibited a low melting point (Tm) and high enthalpy of fusion (∆Hm) of 35.7 °C and 43.9 J g-1, respectively, making it a potential candidate for an ambient temperature adjustment textile phase change material (PCM). Polybutylene terephthalate (PBT) was selected as the matrix and blended at different weight ratios of PBHA-C5, and the blended samples showed comparable Tm and ∆Hm after three cycles of cooling and reheating, indicating good maintenance of their phase changing ability. Samples were then processed via melt spinning with a take-up speed of 200 m min-1 at draw ratios (DR) of 1.0 to 3.0 at 50 °C. The fiber's mechanical strength could be enhanced to 2.35 g den-1 by increasing the DR and lowering the PBHA-C5 content. Infrared thermography showed that a significant difference of more than 5 °C between PBT and other samples was achieved within 1 min of heating, indicating the ability of PBHA-C5 to adjust the temperature. After heating for 30 min, the temperatures of neat PBT, blended samples with 27, 30, and 33 wt% PBHA-C5, and neat PBHA-C5 were 53.8, 50.2, 48.3, 47.2, and 46.5 °C, respectively, and reached an equilibrium state, confirming the temperature adjustment ability of PBHA-C5 and suggesting that it can be utilized in thermoregulating applications.
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Oral squamous cell carcinoma (OSCC) affects tens of thousands of people worldwide. Despite advances in cancer treatment, the 5-year survival rate of patients with late-stage OSCC is low at 50-60%. Therefore, the development of anti-OSCC therapy is necessary. We evaluated the effects of marine-derived triterpene stellettin B in human OC2 and SCC4 cells. Stellettin B dose-dependently decreased the viability of both cell lines, with a significant reduction in OC2 cells at ≥0.1 µM at 24 and 48 h, and in SCC4 cells at ≥1 µM at 24 and 48 h. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells were significantly observed at 20 µM of stellettin B at 48 h, with the overexpression of cleaved caspase3 and cleaved poly(ADP-ribose) polymerase (PARP). Moreover, mitochondrial respiratory functions were ablated by stellettin B. Autophagy-related LC3-II/LC3-I ratio and Beclin-1 proteins were increased, whereas p62 was decreased. At 20 µM at 48 h, the expression levels of the endoplasmic reticulum (ER) stress biomarkers calnexin and BiP/GRP78 were significantly increased and mitogen-activated protein kinase (MAPK) signaling pathways were activated. Further investigation using the autophagy inhibitor 3-methyladenine (3-MA) demonstrated that it alleviated stellettin B-induced cell death and autophagy. Overall, our findings show that stellettin B induces the ER stress, mitochondrial stress, apoptosis, and autophagy, causing cell death of OSCC cells.
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Carcinoma de Células Escamosas , Neoplasias de la Boca , Triterpenos , Apoptosis , Autofagia , Carcinoma de Células Escamosas/tratamiento farmacológico , Estrés del Retículo Endoplásmico , Humanos , Neoplasias de la Boca/tratamiento farmacológico , Transducción de Señal , Triterpenos/farmacologíaRESUMEN
INTRODUCTION: The coronavirus 2019 (COVID-19) pandemic has created significant burden on healthcare systems throughout the world. Syndromic surveillance, which collects real-time data based on a range of symptoms rather than laboratory diagnoses, can help provide timely information in emergency response. We examined the effectiveness of a web-based COVID-19 symptom checking tool (C19Check) in the state of Georgia (GA) in predicting COVID-19 cases and hospitalizations. METHODS: We analyzed C19Check use data, COVID-19 cases, and hospitalizations from April 22-November 28, 2020. Cases and hospitalizations in GA were extracted from the Georgia Department of Public Health data repository. We used the Granger causality test to assess whether including C19Check data can improve predictions compared to using previous COVID-19 cases and hospitalizations data alone. Vector autoregression (VAR) models were fitted to forecast cases and hospitalizations from November 29 - December 12, 2020. We calculated mean absolute percentage error to estimate the errors in forecast of cases and hospitalizations. RESULTS: There were 25,861 C19Check uses in GA from April 22-November 28, 2020. Time-lags tested in Granger causality test for cases (6-8 days) and hospitalizations (10-12 days) were significant (P= <0.05); the mean absolute percentage error of fitted VAR models were 39.63% and 15.86%, respectively. CONCLUSION: The C19Check tool was able to help predict COVID-19 cases and related hospitalizations in GA. In settings where laboratory tests are limited, a real-time, symptom-based assessment tool can provide timely and inexpensive data for syndromic surveillance to guide pandemic response. Findings from this study demonstrate that online symptom-checking tools can be a source of data for syndromic surveillance, and the data may help improve predictions of cases and hospitalizations.