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INTRODUCTION: Vortioxetine is an antidepressant with a multimodal mechanism of action. It is used as a treatment option for patients with major depressive episodes. There have only been two previously reported non-fatal overdoses of vortioxetine; neither of these were analytically confirmed There has also been one case of serotonin syndrome potentially related to vortioxetine and two deaths where vortioxetine was detected. We report here a non-fatal analytically confirmed case of vortioxetine overdose. CASE REPORT: A 32-year-old male presented to the emergency department (ED) 12-13 h after oral ingestion of 1,260 mg of vortioxetine and 350 mg of diazepam. A family member reported that he had been drowsy after the overdose, but his level of consciousness and observations (heart rate, blood pressure and temperature) were normal on review by the pre-hospital emergency services and on arrival to the ED. During a period of observation, he did not develop any features of serotonin syndrome or any other significant toxicity. Toxicological analysis of a blood sample taken in the ED detected vortioxetine (plasma concentration 457 ng/mL 10 h after ingestion) and sub-therapeutic concentrations of diazepam and pregabalin. DISCUSSION: Despite having a plasma vortioxetine concentration nearly 15-times therapeutic vortioxetine concentrations, this patient did not develop any significant toxicity. In particular he did not develop any clinical or biochemical features of serotonin toxicity that would be expected with this class of antidepressant. Additional reporting of analytically confirmed vortioxetine overdoses will allow clinicians and licensing authorities to further understand the safety of this medication in overdose.
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The assessment of biodegradable materials, such as bioactive glass, under the existing ISO 10993 standard test methods poses a significant challenge due to potential cell viability impairment caused by the accumulation of degraded products in a static environment. Therefore, innovative methodologies are urgently needed to tailor the unique biodegradation characteristics of these materials, providing more precise and scientific insights into biosafety and efficacy verification. Motivation by its bidirectional regulation of angiogenesis and immunity, zinc (Zn) was incorporated into sol-gel-derived borosilicate bioactive glasses (SBSGs) to fabricate Zn-incorporated borosilicate bioactive glasses (SBSG-Zn) to complement the tissue repair capabilities of bioactive glasses. Both SBSG and SBSG-Zn glasses consist of nanosized particles, slit mesoporous pores, high specific surface areas, and bioreactivity. In vitro comparative analysis, conducted according to ISO 10993 standards, demonstrates that only at suitable dilution ratesâsuch as the 8-fold dilution employed in this studyâdo extracts of SBSG and SBSG-Zn glasses exhibit low cytotoxicity when cultured with human umbilical vein endothelial cells (HUVECs). Notably, SBSG-Zn glasses show optimal promotion of angiogenic gene expression in HUVECs. Furthermore, within an appropriate concentration range of released ions, SBSG-Zn glass extracts not only promote cell survival but also modulate the expression of anti-inflammatory genes while simultaneously inhibiting pro-inflammatory genes concurrently. After being implanted in rat subcutaneous defect models, both SBSG and SBSG-Zn glasses demonstrated the local immunoregulation and angiogenic effects. SBSG-Zn stands out by demonstrating superior modulation of M1/M2 polarization in macrophages as validated by altered secretion of key factors in macrophages and expression of relevant growth factors in HUVECs. These findings underscore the potential for convenient manipulation of localized angiogenic and immunoregulation through the incorporation of zinc into bioactive glass, emphasizing the importance of ensuring the appropriate ion doses are applied for achieving optimal therapeutic efficiency.
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Background The Applied Public Health Informatics Competency Model lists "data analysis, visualization, and reporting" as one of the eight competencies when teaching public health informatics. Thus, public health informatics students need to develop knowledge and skills in visualizing public health data. Unfortunately, there is limited work that discusses pedagogical principles that could guide the implementation of pedagogical activities related to data visualization in public health informatics. Objective To introduce, discuss, and reflect on pedagogical principles that were implemented for a data visualization project in an undergraduate public health informatics course. Method A reflective teaching approach was used to guide the discussion and reflection on how pedagogical principles were implemented for a data visualization project in an undergraduate public health informatics course. The generic implementation framework (i.e., pre-implementation, implementation, and post-implementation) was used to organize the discussion of the course's implementation. Implementation Four pedagogical principles were implemented as part of a data visualization project in an undergraduate public health informatics course: scaffolding (i.e., outputs build on top of each other), constructivism (i.e., students apply knowledge and work in teams to create a dashboard), critical consciousness (i.e., embedding social determinants of health in their dashboard), and equity and inclusion (i.e., using a free data visualization software that is easy to use for beginners and is used by public health institutions). Post-implementation reflection revealed areas of improvement, such as enhancing group advising, adding more SDOH variables in the dashboard, and plans for scalability. Conclusion A data visualization project in an undergraduate public health informatics course could benefit from implementing multiple pedagogical principles. Overall, creating dashboards can be a learning tool to enhance data visualization skills among undergraduate public health informatics students. Dashboards can also emphasize the impact of health disparities and inequities in public health by incorporating principles of social determinants of health.
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Images collected during NASA's Double Asteroid Redirection Test (DART) mission provide the first resolved views of the Didymos binary asteroid system. These images reveal that the primary asteroid, Didymos, is flattened and has plausible undulations along its equatorial perimeter. At high elevations, its surface is rough and contains large boulders and craters; at low elevations its surface is smooth and possesses fewer large boulders and craters. Didymos' moon, Dimorphos, possesses an intimate mixture of boulders, several asteroid-wide lineaments, and a handful of craters. The surfaces of both asteroids include boulders that are large relative to their host body, suggesting that both asteroids are rubble piles. Based on these observations, our models indicate that Didymos has a surface cohesion ≤ 1 Pa and an interior cohesion of â¼10 Pa, while Dimorphos has a surface cohesion of <0.9 Pa. Crater size-frequency analyzes indicate the surface age of Didymos is 40-130 times older than Dimorphos, with likely absolute ages of ~ 12.5 Myr and <0.3 Myr, respectively. Solar radiation could have increased Didymos' spin rate leading to internal deformation and surface mass shedding, which likely created Dimorphos.
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Bioelectronic therapies modulating the vagus nerve are promising for cardiovascular, inflammatory, and mental disorders. Clinical applications are however limited by side-effects such as breathing obstruction and headache caused by non-specific stimulation. To design selective and functional stimulation, we engineered VaStim, a realistic and efficient in-silico model. We developed a protocol to personalize VaStim in-vivo using simple muscle responses, successfully reproducing experimental observations, by combining models with trials conducted on five pigs. Through optimized algorithms, VaStim simulated the complete fiber population in minutes, including often omitted unmyelinated fibers which constitute 80% of the nerve. The model suggested that all Aα-fibers across the nerve affect laryngeal muscle, while heart rate changes were caused by B-efferents in specific fascicles. It predicted that tripolar paradigms could reduce laryngeal activity by 70% compared to typically used protocols. VaStim may serve as a model for developing neuromodulation therapies by maximizing efficacy and specificity, reducing animal experimentation.
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Simulación por Computador , Estimulación del Nervio Vago , Nervio Vago , Animales , Porcinos , Nervio Vago/fisiología , Estimulación del Nervio Vago/métodos , Frecuencia Cardíaca/fisiología , AlgoritmosRESUMEN
PURPOSE: This Aotearoa New Zealand-based study addresses a gap in literature focusing on individual experiences of racism among adolescents and young adults and its links to health. METHODS: This cross-sectional study uses data from multiple instances of the New Zealand Health Survey (2002/03, 2006/07, 2011/12, 2016/17) and General Social Survey (2008-2016) restricted to participants aged 15-24 years. Prevalence of reported experiences of racism are estimated. Meta-analytic techniques to pool data and multiple regression analyses are used to examine associations between experiences of racism and outcomes measures (mental and physical health, general health and well-being, life satisfaction, inability to access health care, and identity). The study used an ethical co-design process between university researchers and a rangatahi Maori (Maori young people) partnership group. RESULTS: Racism was higher among Maori, Pacific, and Asian young people compared to European young people. Racism was associated with all negative health and well-being measures examined for young people, including negative mental and physical health measures (12-Item Short Form Survey, Kessler Psychological Distress Scale), lower self-rated health, negative life satisfaction, higher unmet need for primary care, and identity measures (feelings of not belonging in New Zealand, less able to express their identity). DISCUSSION: The results of this study are concerning. Non-European young people disproportionately bear the burden of racism in Aotearoa New Zealand with a potentially substantial impact on their health and well-being. This is a breach of Indigenous (for Maori) and other international human rights and should be motivation to act to eliminate racism in all its forms.
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Racismo , Humanos , Nueva Zelanda , Adolescente , Racismo/psicología , Masculino , Adulto Joven , Femenino , Estudios Transversales , Estado de Salud , Encuestas Epidemiológicas , Nativos de Hawái y Otras Islas del Pacífico/psicología , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Salud Mental , Accesibilidad a los Servicios de SaludRESUMEN
A continuous levodopa sensor can improve the quality of life for patients suffering with Parkinson's disease by enhancing levodopa titration and treatment effectiveness; however, its development is currently hindered by the absence of a specific levodopa molecular recognition element and limited insights into how real-time monitoring might affect clinical outcomes. This gap in research contributes to clinician uncertainty regarding the practical value of continuous levodopa monitoring data. This paper examines the current state of levodopa sensing and the inherent limitations in today's methods. Further, these challenges are described, including aspects such as interference from the metabolic pathway and adjunct medications, temporal resolution, and clinical questions, with a specific focus on a comprehensive selection of molecules, such as adjunct medications and structural isomers, as an interferent panel designed to assess and validate future levodopa sensors. We review insights and lessons from previously reported levodopa sensors and present a comparative analysis of potential molecular recognition elements, discussing their advantages and drawbacks.
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Levodopa , Enfermedad de Parkinson , Levodopa/análisis , Levodopa/química , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/diagnóstico , Antiparkinsonianos/uso terapéutico , Monitoreo de Drogas/métodosRESUMEN
OBJECTIVE: The 1940 Census is a valuable resource for understanding various aspects of historical populations in the United States. Recently, the National Social Life, Health and Aging Project (NSHAP) integrated 1940 Census data into its extensive dataset, providing researchers with an opportunity to explore new avenues of life course investigation. We leverage the newly-introduced measures of childhood residential environment and evaluate their potential predictive utility in older adult cognitive functioning net of childhood and adulthood characteristics known to be key risk factors for poor cognition. METHOD: We analyzed 777 respondents who were children in 1940 (age<17) that have been linked to the 1940 U.S. Census. We used childhood geographic location, homeownership status, household composition, and parental nativity as predictors. Cognitive function was measured using the Montreal Cognitive Assessment. RESULTS: Regression analysis showed that growing up in an urban area was associated with better cognitive function, while being born in the South was linked to poorer cognitive function, even after controlling for childhood health, parental education, educational attainment, stroke, and smoking status. Additionally, childhood multigenerational household was associated with better cognitive function, and childhood family size was associated with poorer cognitive function. However, these associations became statistically insignificant with the inclusion of educational attainment. We did not find homeownership and parental nativity to be associated with cognitive function. DISCUSSION: The findings may shed light on the potential long-term effects of childhood circumstances on cognitive aging processes. Implications for current literature and directions for future research are discussed.
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Human parainfluenza virus type 3 (HPIV3) is a major pediatric respiratory pathogen lacking available vaccines or antiviral drugs. We generated live-attenuated HPIV3 vaccine candidates by codon-pair deoptimization (CPD). HPIV3 open reading frames (ORFs) encoding the nucleoprotein (N), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin-neuraminidase (HN), and polymerase (L) were modified singly or in combination to generate 12 viruses designated Min-N, Min-P, Min-M, Min-FHN, Min-L, Min-NP, Min-NPM, Min-NPL, Min-PM, Min-PFHN, Min-MFHN, and Min-PMFHN. CPD of N or L severely reduced growth in vitro and was not further evaluated. CPD of P or M was associated with increased and decreased interferon (IFN) response in vitro, respectively, but had little effect on virus replication. In Vero cells, CPD of F and HN delayed virus replication, but final titers were comparable to wild-type (wt) HPIV3. In human lung epithelial A549 cells, CPD F and HN induced a stronger IFN response, viral titers were reduced 100-fold, and the expression of F and HN proteins was significantly reduced without affecting N or P or the relative packaging of proteins into virions. Following intranasal infection in hamsters, replication in the nasal turbinates and lungs tended to be the most reduced for viruses bearing CPD F and HN, with maximum reductions of approximately 10-fold. Despite decreased in vivo replication (and lower expression of CPD F and HN in vitro), all viruses induced titers of serum HPIV3-neutralizing antibodies similar to wt and provided complete protection against HPIV3 challenge. In summary, CPD of HPIV3 yielded promising vaccine candidates suitable for further development.
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Codón , Virus de la Parainfluenza 3 Humana , Vacunas Atenuadas , Replicación Viral , Animales , Virus de la Parainfluenza 3 Humana/inmunología , Virus de la Parainfluenza 3 Humana/genética , Humanos , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/genética , Codón/genética , Cricetinae , Infecciones por Respirovirus/inmunología , Infecciones por Respirovirus/prevención & control , Infecciones por Respirovirus/virología , Chlorocebus aethiops , Células Vero , Sistemas de Lectura Abierta/genética , Mesocricetus , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Vacunas Virales/inmunología , Vacunas Virales/genética , Proteínas Virales/inmunología , Proteínas Virales/genética , Vacunas contra la Parainfluenza/inmunología , Vacunas contra la Parainfluenza/genéticaRESUMEN
We present and demonstrate a method to produce quantitative and qualitative descriptions of transient dynamics from empirical data, with the purpose of analyzing a novel transient discovered in liquid crystal electroconvection. By constructing a tensor bundle around an exemplar transient and creating a chart at every step aligned with the direction of propagation, we show that the Jacobian estimation problem can be reduced by a single dimension, relaxing data requirements and clarifying results. We apply this analysis to identify the onset of a boundary crisis in a predator-prey model. The resulting tensor bundle estimated from image data taken during a dynamical phase transition in a nematic liquid crystal details the behavior of the system along that trajectory, allowing topological analysis. Using this method, we quantify a saddle point in the phase space that drives the initial dynamics during a sudden increase in the driving voltage.
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Parasitic neglected tropical diseases, such as schistosomiasis and soil-transmitted helminthiasis (STH), remain as significant public health concerns in developing countries such as the Philippines. This study aimed to determine the prevalence and intensity of schistosomiasis and STH among school-age children (SAC) and adults in two co-endemic provinces in Mindanao in southern Philippines as part of monitoring of national control programs. Stool samples were collected, processed using Kato-Katz technique, and examined microscopically for presence of intestinal helminth ova. A total of 776 SAC and 526 adults participated in the study. Low schistosomiasis prevalence was generally observed in SAC (0.8%) and adults (0.4%). Generally low STH prevalence was reported in both SAC (3.9%) and adults (3.4%). Only three SAC had heavy intensity STH, which was not seen in adults. Results indicate a state of good morbidity control, which may be a result of effective implementation of mass drug administration (MDA) strategy for schistosomiasis, STH, and lymphatic filariasis in the last several years. The low prevalence and intensities of infections may also be partly attributed to the low diagnostic sensitivity of Kato-Katz technique in detecting low intensity intestinal helminth infections. While results of this study also indicate similarly low levels of both these infections in previous studies, sustaining high MDA coverage rates and addressing remaining challenges related to intensified case finding and treatment, improvements in safe water, sanitation, and hygiene, veterinary public health, and vector ecology and management will be necessary to interrupt transmission in these areas.
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Heces , Helmintiasis , Esquistosomiasis , Suelo , Filipinas/epidemiología , Humanos , Prevalencia , Helmintiasis/epidemiología , Helmintiasis/transmisión , Niño , Esquistosomiasis/epidemiología , Esquistosomiasis/transmisión , Adulto , Suelo/parasitología , Femenino , Masculino , Adolescente , Heces/parasitología , Adulto Joven , Animales , Persona de Mediana Edad , Administración Masiva de MedicamentosRESUMEN
Gritti-Stokes amputation (GSA) is a knee disarticulation variant, where the femur is transected at the level of the epicondyle and the patella is fixated to the distal end. GSA results in a long residual limb with little postoperative swelling and less potential for muscular atrophy, so stable limb volume may allow the use of seal-in suction for suspension for preparatory prostheses. The purpose of this case series was to report on the efficacy of seal-in suction preparatory prostheses for 2 adults with traumatic GSA. Between October and December of 2021, 2 participants with unilateral traumatic Gritti-Stokes amputation, who had received seal-in suction suspension for their preparatory prostheses, were recruited. Information was extracted from medical charts regarding prosthetic care and mobility at preparatory and definitive prosthesis evaluation, and participants underwent standardized measurement of their residual limb and prosthesis. Duration of preparatory prosthesis use was >6 months; neither participant reported loss of suspension nor significant complications with socket fit. Participant 1 required socket replacement because of residual limb pain secondary to osteophyte formation, and Participant 2 required component replacement because of weight gain. At definitive prosthesis evaluations, both participants were unlimited community ambulators; both successfully returned to work before provision of their definitive prostheses. Results indicate that seal-in suction suspension may be viable for preparatory prostheses among adults with traumatic GSA, but knee center height discrepancies persist. GSA may yield highly functional outcomes for adults with traumatic amputation. Further research is required to substantiate these findings.
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Aim: Recent data have identified specific symptom and polysomnographic profiles associated with cardiovascular disease (CVD) in patients with obstructive sleep apnoea (OSA). Our aim was to determine whether these profiles were present at diagnosis of OSA in patients with established CVD and in those with high cardiovascular risk. Participants in the Sydney Sleep Biobank (SSB) database, aged 30-74 years, self-reported presence of CVD (coronary artery disease, cerebrovascular disease, or heart failure). In those without established CVD, the Framingham Risk Score (FRS) estimated 10-year absolute CVD risk, categorised as "low" (<6%), "intermediate" (6-20%), or "high" (>20%). Groups were compared on symptom and polysomnographic variables. Results: 629 patients (68% male; mean age 54.3 years, SD 11.6; mean BMI 32.3 kg/m2, SD 8.2) were included. CVD was reported in 12.2%. A further 14.3% had a low risk FRS, 38.8% had an intermediate risk FRS, and 34.7% had a high risk FRS. Groups differed with respect to age, sex and BMI. OSA severity increased with established CVD and increasing FRS. The symptom of waking too early was more prevalent in the higher FRS groups (p=0.004). CVD and FRS groups differed on multiple polysomnographic variables; however, none of these differences remained significant after adjusting for age, sex, and BMI. Conclusion: Higher CVD risk was associated with waking too early in patients with OSA. Polysomnographic variations between groups were explained by demographic differences. Further work is required to explore the influence of OSA phenotypic characteristics on susceptibility to CVD.
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The cortical anthraquinone yellow-orange pigment parietin is a secondary lichen substance providing UV-shielding properties that is produced by several lichen species. In our work, the secondary metabolite has been extracted from air-dried thalli of Xanthoria parietina. The aims of this study were to characterize parietin absorbance through UV-VIS spectrophotometry and with IR spectroscopy and to evaluate its photodegradability under UV radiation through in situ reflectance IR spectroscopy to understand to what extent the substance may have a photoprotective role. This allows us to relate parietin photo-degradability to the lichen UV tolerance in its natural terrestrial habitat and in extreme environments relevant for astrobiology such as Mars. Extracted crystals were UV irradiated for 5.59 h under N2 flux. After the UV irradiation, we assessed relevant degradations in the 1614, 1227, 1202, 1160 and 755 cm-1 bands. However, in light of Xanthoria parietina survivability in extreme conditions such as space- and Mars-simulated ones, we highlight parietin UV photo-resistance and its relevance for astrobiology as photo-protective substance and possible bio-hint.
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Emodina/análogos & derivados , Exobiología , Líquenes , Rayos Ultravioleta , Líquenes/efectos de la radiación , Líquenes/química , Fotólisis , Espectrofotometría InfrarrojaRESUMEN
BACKGROUND: Dengue has become a major health issue in tropical regions as the numbers of reported cases and estimated infections continuously increase. In the Philippines, many challenges remain in preventing and controlling the disease amidst all the mitigation efforts of the government. This study sought to measure the health literacy of Filipino teachers and determine the associations among teachers' knowledge, attitudes, and selected practices (KAP) against dengue. METHODS: Elementary and secondary school teachers from the consistently declared dengue hotspots in the City of San Fernando, Pampanga, Philippines, from the years 2017 to 2019 were selected as target participants in this cross-sectional study. A self-administered online survey tool was used in this study for both screening of participants and the KAP survey proper. STATA, descriptive statistics, and multiple logistic regression were used for the data analysis. Odds Ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS: The study comprised 604 participants whose mean age was 38.4 years. Television was determined as the top media source of information, and various health staff were the most trusted and common source of information. Good knowledge on dengue treatment (OR = 1.81; 95% CI 1.18-2.78) and dengue prevention (OR = 1.85; 95% CI 1.26-2.71) were positively associated with having good practices on protection against mosquito bites. Good knowledge on dengue signs and symptoms (OR = 1.56; 95% CI 1.02-2.37) and dengue prevention (OR = 2.38; 95% CI 1.59-3.58) were positively associated with having good practices on preventing breeding sites. Those with positive perceived susceptibility to dengue had lower odds of having good practices on protection against mosquito bites (OR = 0.64; 95% CI 0.41-0.99) and of having good practices on preventing breeding sites (OR = 0.46; 95% CI 0.26-0.81). CONCLUSION: Even with the existing dengue policies, programs, and strategies, and the high disease literacy rate of Filipinos, dengue remains a struggle with an increasing case rate. Therefore, specific concepts should be emphasized, and interventions should be fine-tuned to better reach and influence the target population to attain a dengue-free Philippines.
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OBJECTIVE: The aim of this study was to evaluate the prevalence of, and explore factors related to, prescription of potentially inappropriate medications (PIMs) among older adults with lower-limb loss (LLL). METHODS: This was a secondary analysis of a cross-sectional dataset collected through an interdisciplinary limb loss clinic between September 2013 and November 2022. Self-report medication lists were reviewed during in-clinic face-to-face interviews and compared to the American Geriatrics Society Beers Criteria corresponding to the patient's evaluation year. RESULTS: Of 82 participants (72.9 ± 6.6 years-old; 78.0 % male), n = 41 (50.0 %) reported using one or more PIM. PIM prescription was significantly associated with presence of phantom limb pain, history of upper gastrointestinal issues, and a greater number of medications. DISCUSSION: Polypharmacy and PIM use are common among older adults with LLL. Greater attention should be paid to medications post-amputation, especially pain management medications, to minimize potential adverse side-effects.
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Geriatría , Lista de Medicamentos Potencialmente Inapropiados , Humanos , Masculino , Anciano , Femenino , Prescripción Inadecuada , Estudios Transversales , PolifarmaciaRESUMEN
Metal-organic frameworks (MOFs) have a high specific surface area, adjustable pores and can be used to obtain functional porous materials with diverse and well-ordered structures through coordination and self-assembly, which has intrigued wide interest in a broad range of disciplines. In the arena of biomedical engineering, the functionalized modification of MOFs has produced drug carriers with excellent dispersion and functionalities such as target delivery and response release, with promising applications in bio-detection, disease therapy, tissue healing, and other areas. This review summarizes the present state of research on the functionalization of MOFs by physical binding or chemical cross-linking of small molecules, polymers, biomacromolecules, and hydrogels and evaluates the role and approach of MOFs functionalization in boosting the reactivity of materials. On this basis, research on the application of functionalized MOFs composites in biomedical engineering fields such as drug delivery, tissue repair, disease treatment, bio-detection and imaging is surveyed, and the development trend and application prospects of functionalized MOFs as an important new class of biomedical materials in the biomedical field are anticipated, which may provide some inspiration and reference for further development of MOF for bio-medical applications.
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Accumulation of the ribonucleoside, adenosine (ADO), triggers a cAMP response element binding protein (CREB)-mediated signaling pathway to suppress the function of immune cells in tumors. Here, we describe a collection of CREB-activated promoters that allow for strong and tunable ADO-induced gene expression in human cells. By optimizing number of CREB transcription factor binding sites and altering the core promoter region of CREB-based hybrid promoters, we created synthetic constructs that drive gene expression to higher levels than strong, endogenous mammalian promoters in the presence of ADO. These synthetic promoters are induced up to 47-fold by ADO, with minimal expression in their "off" state. We further determine that our CREB-based promoters are activated by other compounds that act as signaling analogs, and that combinatorial addition of ADO and these compounds has a synergistic impact on gene expression. Surprisingly, we also detail how background ADO degradation caused by the common cell culture media additive, fetal bovine serum (FBS), confounds experiments designed to determine ADO dose-responsiveness. We show that only after long-term heat deactivation of FBS can our synthetic promoters enable gene expression induction at physiologically relevant levels of ADO. Finally, we demonstrate that the strength of a CREB-based promoter is enhanced by incorporating other transcription factor binding sites.
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Adenosina , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Animales , Humanos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Adenosina/genética , AMP Cíclico/metabolismo , Regiones Promotoras Genéticas/genética , Expresión Génica , Transcripción Genética , Mamíferos/genéticaRESUMEN
ISSUE ADDRESSED: Aboriginal and Torres Strait Islander child ear health is complex and multiple. We examined relationships between parent-reported sociodemographic, child health, health service access factors and ear symptoms among Aboriginal and Torres Strait Islander children aged 3 to 7 years. METHODS: The Longitudinal Study of Indigenous Children is a large child cohort study with annual parent-reported data collection. Generalised linear mixed model analyses examined Wave 1 (1309 children 0-5 years; 2008) predictors of being free of parent-reported ear symptoms in both Waves 2 and 3. RESULTS: A total of 1030 (78.7%) had no reported ear symptoms in either Wave 2 or 3. In the fully adjusted model, children who had been hospitalised in the past year (aOR = 2.16; 95% CI 1.19-3.93) and those with no ear symptoms (aOR = 2.94; 95% CI, 1.59-5.46) at Wave 1 had higher odds of no ear symptoms in both the subsequent waves. There were also relationships between parent main source of income-government pension or allowance as well as parents who reported no history of their own ear symptoms and higher odds of no ear symptoms in Waves 2 and 3 after partial adjustment for sociodemographic factors. CONCLUSION: These findings suggest relationships between different sociodemographic and health factors and parent-reported ear symptoms among Aboriginal and Torres Strait Islander children that warrant further investigation. So what? Children with parent-reported ear symptoms during the early years need holistic support to prevent future ear symptoms that impact health, social and educational life trajectories.