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Children with autism from underserved communities face complex system-, provider-, and family-level barriers to accessing timely diagnosis and early intervention. The current study evaluated the preliminary effects and feasibility of a new program (ECHO Autism LINKS) that integrated pediatric primary care provider (PCP) training with family navigation (FN) to bridge the gaps between screening, referral, and service access. Three cohorts of PCPs (n = 42) participated in the program, which consisted of 60-minute sessions delivered by Zoom twice per month for 12 months. Each session included didactics, case-based learning, and collaborative discussion with participants and an interdisciplinary team of experts. Family navigators were members of the expert team and provided FN services to families referred by PCP participants. Program attendance and engagement were strong, with 40 cases presented and 258 families referred for FN services, most of whom (83%) needed help accessing and connecting with services, and 13% required ongoing support due to complex needs. PCPs demonstrated significant improvements in self-efficacy in providing best-practice care for children with autism, reported high satisfaction, and observed improved knowledge and practice as a result of the program. The results of this initial pilot provide support for the feasibility, acceptability, and preliminary efficacy of the ECHO Autism LINKS program. The model holds promise in addressing complex barriers to healthcare access by providing both PCPs and families with the knowledge and support they need. Future research is needed to evaluate the efficacy and effectiveness of the program in improving child and family outcomes.
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Women with domestic violence experiences often refuse to seek help face-to-face due to embarrassment. They begin to share their emotions and seek help from online health communities. Understanding and responding to these posts can be crucial in providing timely support to the victims. We proposed a fine-tuned large language model (LLM) capable of accurately predicting the informational need based on the content of postings. We fine-tuned the LAMMA2-7B-chat model based on the guidance of identifying the information need and a dataset comprising 273 posts from Reddit, which are manually annotated by domain experts. Furthermore, we evaluated the performance of our model using a random sample of 15 posts, and 66.6% were accurately predicted. The results demonstrate that our model can rapidly capture the information needs expressed in the posts, enabling healthcare providers to provide timely and useful support based on our predictions.
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Violência Doméstica , Sobreviventes , Humanos , Sobreviventes/psicologia , Feminino , Processamento de Linguagem Natural , Mídias Sociais , Avaliação das NecessidadesRESUMO
The heart beats approximately 100,000 times per day in humans, imposing substantial energetic demands on cardiac muscle. Adenosine triphosphate (ATP) is an essential energy source for normal function of cardiac muscle during each beat, as it powers ion transport, intracellular Ca2+ handling, and actin-myosin cross-bridge cycling. Despite this, the impact of excitation-contraction coupling on the intracellular ATP concentration ([ATP]i) in myocytes is poorly understood. Here, we conducted real-time measurements of [ATP]i in ventricular myocytes using a genetically encoded ATP fluorescent reporter. Our data reveal rapid beat-to-beat variations in [ATP]i. Notably, diastolic [ATP]i was <1 mM, which is eightfold to 10-fold lower than previously estimated. Accordingly, ATP-sensitive K+ (KATP) channels were active at physiological [ATP]i. Cells exhibited two distinct types of ATP fluctuations during an action potential: net increases (Mode 1) or decreases (Mode 2) in [ATP]i. Mode 1 [ATP]i increases necessitated Ca2+ entry and release from the sarcoplasmic reticulum (SR) and were associated with increases in mitochondrial Ca2+. By contrast, decreases in mitochondrial Ca2+ accompanied Mode 2 [ATP]i decreases. Down-regulation of the protein mitofusin 2 reduced the magnitude of [ATP]i fluctuations, indicating that SR-mitochondrial coupling plays a crucial role in the dynamic control of ATP levels. Activation of ß-adrenergic receptors decreased [ATP]i, underscoring the energetic impact of this signaling pathway. Finally, our work suggests that cross-bridge cycling is the largest consumer of ATP in a ventricular myocyte during an action potential. These findings provide insights into the energetic demands of EC coupling and highlight the dynamic nature of ATP concentrations in cardiac muscle.
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Trifosfato de Adenosina , Cálcio , Acoplamento Excitação-Contração , Ventrículos do Coração , Miócitos Cardíacos , Miócitos Cardíacos/metabolismo , Trifosfato de Adenosina/metabolismo , Acoplamento Excitação-Contração/fisiologia , Animais , Cálcio/metabolismo , Ventrículos do Coração/metabolismo , Ventrículos do Coração/citologia , Potenciais de Ação/fisiologia , Retículo Sarcoplasmático/metabolismo , Frequência Cardíaca/fisiologia , Humanos , Canais KATP/metabolismo , Contração Miocárdica/fisiologia , CamundongosRESUMO
Delivering COVID-19 vaccines with 4-6 weeks shelf life remains one of Africa's most pressing challenges. The Africa Centres for Disease Control and Prevention (Africa CDC) leadership recognised that COVID-19 vaccines donated to many African countries were at risk of expiry considering the short shelf life on delivery in the Member States and slow vaccine uptake rates. Thus, a streamlined rapid response system, the urgent support mechanism, was developed to assist countries accelerate COVID-19 vaccine uptake. We describe the achievements and lessons learnt during implementation of the urgent support mechanism in eight African countries. An Africa CDC team was rapidly deployed to meet with the Ministry of Health of each country alerted for COVID-19 vaccine expiry and identified national implementing partners to quickly develop operational work plans and strategies to scale up the urgent use of the vaccines. The time between the initiation of alerts to the start of the implementation was typically within 2 weeks. A total of approximately 2.5 million doses of vaccines, costing $900 000, were prevented from expiration. The urgent support has also contributed to the increased COVID-19 vaccination coverage in the Member States from 16.1% at the initiation to 25.3% at the end of the urgent support. Some of the effective strategies used by the urgent support mechanism included coordination between Africa CDC and country vaccine task forces, establishment of vaccination centres, building the capacity of routine and surge health workforce, procurement and distribution of vaccine ancillaries, staff training, advocacy and sensitisation events, and use of trusted religious scriptures and community influencers to support public health messages. The urgent support mechanism demonstrated a highly optimised process and serves as a successful example for acceleration and integration of vaccination into different healthcare delivery points.
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Vacinas contra COVID-19 , COVID-19 , Humanos , África , COVID-19/prevenção & controle , Vacinas contra COVID-19/economia , Vacinas contra COVID-19/provisão & distribuição , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Participação da Comunidade , Vacinação/economia , Vacinação/métodosRESUMO
OBJECTIVE: To determine the effect of a single intraoperative dose of dexamethasone on the risk of postoperative reflux (POR) in horses undergoing small intestinal surgery and to investigate its association with incisional complications and short-term survival. DESIGN: Retrospective cohort study over an 11-year period (2008-2019). SETTING: UK-based private referral center. ANIMALS: Two hundred and forty client-owned horses >6 months of age undergoing exploratory laparotomy for treatment of a small intestinal lesion. INTERVENTIONS: Ninety-seven horses received a single intraoperative dose of dexamethasone (0.1 mg/kg, IV). MEASUREMENTS AND MAIN RESULTS: Of 97 horses that received dexamethasone, 52 (53.6%) required small intestinal resection. Of 143 horses that did not receive dexamethasone, small intestinal resection was performed in 78 (54.5%). A total of 70 horses (29%) developed POR. There was no difference in the risk of POR between horses that received dexamethasone (25/97; 26%) and those that did not (45/143; 31%, P = 0.34). Risk factors associated with the development of POR included small intestinal resection (odds ratio [OR]: 4.55, 95% confidence interval [CI]: 2.27-9.11, P < 0.001), a PCV >40% 24 hours postoperatively (OR: 4.11, 95% CI: 2-8.45, P < 0.001), and a WBC count >10 × 109/L on admission (OR: 3.29, 95% CI: 1.47-7.41, P = 0.004). Dexamethasone was not associated with the odds of POR. Horses undergoing repeat laparotomy had a higher risk of incisional infection (OR: 8.07, 95% CI: 1.98-32.81, P = 0.004). Dexamethasone administration was not associated with incisional infection. The development of POR was negatively associated with short-term survival (OR: 0.07, 95% CI: 0.03-0.17, P ≤ 0.001). Dexamethasone administration was not retained in the final multivariable model for survival. CONCLUSIONS: Intraoperative dexamethasone was not associated with the development of POR in this study population, nor did it have an effect on postoperative survival or incisional infection in horses undergoing surgical management of small intestinal disease.
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Dexametasona , Doenças dos Cavalos , Intestino Delgado , Laparotomia , Complicações Pós-Operatórias , Animais , Cavalos , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Estudos Retrospectivos , Doenças dos Cavalos/cirurgia , Feminino , Masculino , Laparotomia/veterinária , Laparotomia/efeitos adversos , Intestino Delgado/cirurgia , Complicações Pós-Operatórias/veterinária , Estudos de Coortes , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Enteropatias/veterinária , Enteropatias/cirurgiaRESUMO
Antarctic marine ectotherms live in the constant cold and are characterised by limited resilience to elevated temperature. Here we tested three of the central paradigms underlying this resilience. Firstly, we assessed the ability of eight species, from seven classes representing a range of functional groups, to survive, for 100 to 303 days, at temperatures 0 to 4 °C above previously calculated long-term temperature limits. Survivors were then tested for acclimation responses to acute warming and acclimatisation, in the field, was tested in the seastar Odontaster validus collected in different years, seasons and locations within Antarctica. Finally, we tested the importance of oxygen limitation in controlling upper thermal limits. We found that four of 11 species studied were able to survive for more than 245 days (245-303 days) at higher than previously recorded temperatures, between 6 and 10 °C. Only survivors of the anemone Urticinopsis antarctica did not acclimate CTmax and there was no evidence of acclimatisation in O. validus. We found species-specific effects of mild hyperoxia (30% oxygen) on survival duration, which was extended (two species), not changed (four species) or reduced (one species), re-enforcing that oxygen limitation is not universal in dictating thermal survival thresholds. Thermal sensitivity is clearly the product of multiple ecological and physiological capacities, and this diversity of response needs further investigation and interpretation to improve our ability to predict future patterns of biodiversity.
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BACKGROUND: Intimate partner violence (IPV) is a serious public health problem associated with countless adverse physical and mental health outcomes. It places an enormous economic and public health burden on communities. The aim of this study was to examine the associations between psychological states (such as depression or hopeless) and help-seeking experiences of IPV survivors after experiencing IPV, based on the Allegheny County Health Survey (ACHS). METHODS: Data from 2015 to 2016 Allegheny County Health Survey with N = 8,012 adults were analyzed. The 6-item version of the Kessler Psychological Stress Scale, located in Module 11 of the ACHS questionnaire, was used to measure psychological stress in participants. Module 12 of the ACHS questionnaire collected information on participants' experiences of intimate partner violence and help-seeking in the past 12 months. Descriptive statistical analysis, Pearson's chi-square or two sample independent t-tests statistical analysis, and multivariate binary logistic regression models were used to analyze the relationship between IPV experience and psychological distress. RESULTS: A total of 212 of the 8,012 participants had IPV experience, with age, marital status, education, income, and race significantly different from those without IPV experience. The psychological stress of participants feeling hopeless (OR = 2.02, 95% CI = 1.37-2.99), restless or fidgety (OR = 1.83, 95% CI = 1.27-2.65), perceiving everything was an effort (OR = 1.55, 95% CI = 1.08-2.22) and worthless (OR = 1.49, 95% CI = 1.01-2.20) was associated with the IPV experience. Help-seeking behaviors of IPV survivors were associated with psychological distress, such as hopelessness (OR = 6.71, 95% CI = 1.38-32.60). CONCLUSIONS: This study explored the association between IPV experience, help-seeking and psychological distress, and the need to expand community support. It is necessary to implement targeted interventions, enhance training of professionals, and promote the identification of early IPV cases as well as collaboration between healthcare and social support departments to reduce the occurrence of IPV or psychological distress following IPV.
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Violência por Parceiro Íntimo , Angústia Psicológica , Adulto , Humanos , Ansiedade , Inquéritos e Questionários , Inquéritos Epidemiológicos , Fatores de RiscoRESUMO
The question of whether artificial intelligence (AI) can be considered conscious and therefore should be evaluated through a moral lens has surfaced in recent years. In this paper, we argue that whether AI is conscious is less of a concern than the fact that AI can be considered conscious by users during human-AI interaction, because this ascription of consciousness can lead to carry-over effects on human-human interaction. When AI is viewed as conscious like a human, then how people treat AI appears to carry over into how they treat other people due to activating schemas that are congruent to those activated during interactions with humans. In light of this potential, we might consider regulating how we treat AI, or how we build AI to evoke certain kinds of treatment from users, but not because AI is inherently sentient. This argument focuses on humanlike, social actor AI such as chatbots, digital voice assistants, and social robots. In the first part of the paper, we provide evidence for carry-over effects between perceptions of AI consciousness and behavior toward humans through literature on human-computer interaction, human-AI interaction, and the psychology of artificial agents. In the second part of the paper, we detail how the mechanism of schema activation can allow us to test consciousness perception as a driver of carry-over effects between human-AI interaction and human-human interaction. In essence, perceiving AI as conscious like a human, thereby activating congruent mind schemas during interaction, is a driver for behaviors and perceptions of AI that can carry over into how we treat humans. Therefore, the fact that people can ascribe humanlike consciousness to AI is worth considering, and moral protection for AI is also worth considering, regardless of AI's inherent conscious or moral status.
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Cardiac dysfunction is a hallmark of aging in humans and mice. Here we report that a two-week treatment to restore youthful Bridging Integrator 1 (BIN1) levels in the hearts of 24-month-old mice rejuvenates cardiac function and substantially reverses the aging phenotype. Our data indicate that age-associated overexpression of BIN1 occurs alongside dysregulated endosomal recycling and disrupted trafficking of cardiac CaV1.2 and type 2 ryanodine receptors. These deficiencies affect channel function at rest and their upregulation during acute stress. In vivo echocardiography reveals reduced systolic function in old mice. BIN1 knockdown using an adeno-associated virus serotype 9 packaged shRNA-mBIN1 restores the nanoscale distribution and clustering plasticity of ryanodine receptors and recovers Ca2+ transient amplitudes and cardiac systolic function toward youthful levels. Enhanced systolic function correlates with increased phosphorylation of the myofilament protein cardiac myosin binding protein-C. These results reveal BIN1 knockdown as a novel therapeutic strategy to rejuvenate the aging myocardium.
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Proteínas Adaptadoras de Transdução de Sinal , Envelhecimento , Miocárdio , Proteínas do Tecido Nervoso , Canal de Liberação de Cálcio do Receptor de Rianodina , Proteínas Supressoras de Tumor , Animais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Masculino , Envelhecimento/metabolismo , Camundongos , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genética , Miocárdio/metabolismo , Miocárdio/patologia , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Técnicas de Silenciamento de Genes , Endossomos/metabolismo , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo L/genética , Coração/fisiopatologia , Camundongos Endogâmicos C57BL , Humanos , Miócitos Cardíacos/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/genética , SístoleRESUMO
People with depression and other neuropsychiatric disorders can experience motivational dysfunctions such as fatigue and anergia, which involve reduced exertion of effort in goal-directed activity. To model effort-related motivational dysfunction, effort-based choice tasks can be used, in which rats can select between obtaining a preferred reinforcer by high exertion of effort vs. a low effort/less preferred option. Preclinical data indicate that dopamine transport (DAT) inhibitors can reverse pharmacologically-induced low-effort biases and increase selection of high-effort options in effort-based choice tasks. Although classical DAT blockers like cocaine can produce undesirable effects such as liability for misuse and psychotic reactions, not all DAT inhibitors have the same neurochemical profile. The current study characterized the effort-related effects of novel DAT inhibitors that are modafinil analogs and have a range of binding profiles and neurochemical actions (JJC8-088, JJC8-089, RDS3-094, and JJC8-091) by using two different effort-related choice behavior tasks in male Sprague-Dawley rats. JJC8-088, JJC8-089, and RDS3-094 significantly reversed the low-effort bias induced by the VMAT-2 inhibitor tetrabenazine, increasing selection of high-effort fixed ratio 5 lever pressing vs. chow intake. In addition, JJC8-089 reversed the effects of tetrabenazine in female rats. JJC8-088 and JJC8-089 also increased selection of high-effort progressive ratio responding in a choice task. However, JJC8-091 failed to produce these outcomes, potentially due to its unique pharmacological profile (i.e., binding to an occluded conformation of DAT). Assessment of a broad range of DAT inhibitors with different neurochemical characteristics may lead to the identification of compounds that are useful for treating motivational dysfunction in humans.
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Proteínas da Membrana Plasmática de Transporte de Dopamina , Motivação , Ratos Sprague-Dawley , Animais , Motivação/efeitos dos fármacos , Motivação/fisiologia , Masculino , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/antagonistas & inibidores , Feminino , Ratos , Comportamento de Escolha/efeitos dos fármacos , Comportamento de Escolha/fisiologia , Modafinila/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Condicionamento Operante/efeitos dos fármacos , Compostos Benzidrílicos/farmacologiaRESUMO
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is one of the leading indications for liver transplantation (LT) in the United States. As with the current obesity epidemic, the incidence of NASH continues to rise. However, the impact of broad utilization of bariatric surgery (BS) for patients with NASH is unknown, particularly in regard to mitigating the need for LT. METHODS: Markov decision analysis was performed to simulate the lives of 20,000 patients with obesity and concomitant NASH who were deemed ineligible to be waitlisted for LT unless they achieved a body mass index (BMI) < 35 kg/m2. Life expectancy following medical weight management (MWM) and sleeve gastrectomy (SG) were estimated. Base case patients were defined as having NASH without fibrosis and a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. RESULTS: Simulated base case analysis patients who underwent SG gained 14.3 years of life compared to patients who underwent MWM. One year after weight loss intervention, 9% of simulated MWM patients required LT compared to only 5% of SG patients. Survival benefit for SG was observed above a BMI of 32.2 kg/m2. CONCLUSION: In this predictive model of 20,000 patients with obesity and concomitant NASH, surgical weight loss is associated with a reduction in the progression of NASH, thereby reducing the need for LT. A reduced BMI threshold of 32 kg/m2 for BS may offer survival benefit for patients with obesity and NASH.
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Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade Mórbida/cirurgia , Obesidade/cirurgia , Redução de Peso , Gastrectomia , Resultado do TratamentoRESUMO
Plant secondary metabolites (PSMs) are produced by plants to overcome environmental challenges, both biotic and abiotic. We were interested in characterizing how autumn seasonality in temperate and subtropical climates affects overall PSM production in comparison to herbivory. Herbivory is commonly measured between spring to summer when plants have high resource availability and prioritize growth and reproduction. However, autumn seasonality also challenges plants as they cope with limited resources and prepare survival for winter. This suggests a potential gap in our understanding of how herbivory affects PSM production in autumn compared to spring/summer. Using meta-analysis, we recorded overall production of 22 different PSM subgroups from 58 published papers to calculate effect sizes from herbivory studies (absence to presence) and temperate to subtropical seasonal studies (summer to autumn), while considering other variables (e.g., plant type, increase in time since herbivory, temperature, and precipitation). We also compared production of five phenolic PSM subgroups - hydroxybenzoic acids, flavan-3-ols, flavonols, hydrolysable tannins, and condensed tannins. We wanted to detect a shared response across all PSMs and found that herbivory increased overall PSM production in herbaceous plants. Herbivory was also found to have a positive effect on individual PSM subgroups, such as flavonol production, while autumn seasonality was found to have a positive effect on flavan-3-ol and condensed tannin production. We discuss how these responses might stem from plants producing some PSMs constitutively, whereas others are induced only after herbivory, and how plants produce metabolites with higher costs only during seasons when other resources for growth and reproduction are less available, while other phenolic PSM subgroups serve more than one function for plants and such functions can be season dependent. The outcome of our meta-analysis is that autumn seasonality changes some PSM production differently from herbivory, and we see value in further investigating seasonality-herbivory interactions with plant chemical defense.
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OBJECTIVE: The objective of this study was to determine hematologic changes of stored caprine whole blood in citrate phosphate dextrose adenine solution over a 28-day period. SAMPLE: Ten 250-mL bags of whole blood were collected from 10 female Boer goats from Louisiana State University's Division of Laboratory Animal Medicine herd. METHODS: 10 healthy blood donor goats were selected, and 250 mL of whole blood was drawn from each and stored at 2.78 °C. At the time of collection and every 7 days for a total of 28 days, samples were obtained from the blood bags to determine biochemical and hematologic values of collected blood. Only 5 of the 10 donors had baseline blood bag samples obtained for biochemical evaluation on day 0. At the end of 28 days, the remaining blood was submitted for aerobic and anaerobic culture. RESULTS: Blood values remained within suitable limits for transfusion and below 1% hemolysis for up to 21 days in most samples. Packed cell volume did not change significantly from day 0 to day 28. Lactate significantly increased over the 28 days, though not as dramatically as expected on the basis of other blood storage studies. pH decreased due to anticoagulant acidity but did not drop below 7. Cultures were negative on all blood bags. CLINICAL RELEVANCE: Changes over time are similar to that in other species, and caprine blood appears biochemically and hematologically stable for up to 21 days in storage. In vivo trials are needed for safety and efficacy.
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Preservação de Sangue , Cabras , Humanos , Animais , Feminino , Preservação de Sangue/veterinária , Glucose , Transfusão de Sangue/veterinária , Eritrócitos , Ácido Láctico , FosfatosRESUMO
The inner ear is the hub where hair cells (HCs) transduce sound, gravity, and head acceleration stimuli to the brain. Hearing and balance rely on mechanosensation, the fastest sensory signals transmitted to the brain. The mechanoelectrical transducer (MET) channel is the entryway for the sound-balance-brain interface, but the channel-complex composition is not entirely known. Here, we report that the mouse utilizes Piezo1 (Pz1) and Piezo2 (Pz2) isoforms as MET-complex components. The Pz channels, expressed in HC stereocilia, and cell lines are co-localized and co-assembled with MET complex partners. Mice expressing non-functional Pz1 and Pz2 at the ROSA26 locus have impaired auditory and vestibular traits that can only be explained if the Pzs are integral to the MET complex. We suggest that Pz subunits constitute part of the MET complex and that interactions with other MET complex components yield functional MET units to generate HC MET currents.
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Orelha Interna , Células Ciliadas Auditivas Internas , Animais , Camundongos , Células Ciliadas Auditivas Internas/metabolismo , Células Ciliadas Auditivas/metabolismo , Estereocílios/metabolismo , Orelha Interna/metabolismo , Audição , Mecanotransdução Celular , Mamíferos/metabolismo , Canais Iônicos/genética , Canais Iônicos/metabolismoRESUMO
The progression and maintenance of cancer characteristics are associated with cellular components linked to the tumor and non-cellular components with pro-tumoral properties. Pharmacological association with antagonists of the cellular components of the tumor, such as anti- and pro-apoptotic drugs, represents a novel adjuvant strategy. In this study, the antiproliferative, pro-apoptotic, and pharmacological effects of the combination of monophosphoester 2-AEH2P with Simvastatin, Coenzyme Q10, the chemotherapeutic drug paclitaxel, and colony-stimulating factor (GM-CSF) were evaluated. Tests were conducted to determine cytotoxic activity using the MTT method, cell cycle phases, and fragmented DNA by flow cytometry, mitochondrial membrane potential, expression of cell markers Bcl2, TNF-α/DR-4, Cytochrome c, caspase 3, and P53, and analysis of drug combination profiles using Synergy Finder 2.0 Software. The results showed a synergistic effect among the combinations, compared to individual treatments with the monophosphoester and other drugs. In addition, there was modulation of marker expression, indicating a pro-apoptotic and immunomodulatory effect of 2-AEH2P. Pharmacological analysis revealed that tumor cells treated with GM-CSF + 2-AEH2P exhibited a synergistic effect, while groups of tumor cells treated with paclitaxel, Coenzyme Q10, and Simvastatin showed additive effects. Furthermore, treatment with the paclitaxel + 2-AEH2P combination (12 h) resulted in a significant reduction in mitochondrial membrane potential. Pharmacological combinations for normal cells did not exhibit deleterious effects compared to mammary carcinomatosis tumor (EAT) cells.
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The progression and maintenance of cancer characteristics are associated with cellular components linked to the tumor and non-cellular components with pro-tumoral properties. Pharmacological association with antagonists of the cellular components of the tumor, such as anti- and pro-apoptotic drugs, represents a novel adjuvant strategy. In this study, the antiproliferative, pro-apoptotic, and pharmacological effects of the combination of monophosphoester 2-AEH2P with Simvastatin, Coenzyme Q10, the chemotherapeutic drug paclitaxel, and colony-stimulating factor (GM-CSF) were evaluated. Tests were conducted to determine cytotoxic activity using the MTT method, cell cycle phases, and fragmented DNA by flow cytometry, mitochondrial membrane potential, expression of cell markers Bcl2, TNF-α/DR-4, Cytochrome c, caspase 3, and P53, and analysis of drug combination profiles using Synergy Finder 2.0 Software. The results showed a synergistic effect among the combinations, compared to individual treatments with the monophosphoester and other drugs. In addition, there was modulation of marker expression, indicating a pro-apoptotic and immunomodulatory effect of 2-AEH2P. Pharmacological analysis revealed that tumor cells treated with GM-CSF + 2-AEH2P exhibited a synergistic effect, while groups of tumor cells treated with paclitaxel, Coenzyme Q10, and Simvastatin showed additive effects. Furthermore, treatment with the paclitaxel + 2-AEH2P combination (12 h) resulted in a significant reduction in mitochondrial membrane potential. Pharmacological combinations for normal cells did not exhibit deleterious effects compared to mammary carcinomatosis tumor (EAT) cells.
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In the Fall of 2020, many universities saw extensive transmission of SARS-CoV-2 among their populations, threatening the health of students, faculty and staff, the viability of in-person instruction, and the health of surrounding communities.1, 2 Here we report that a multimodal "SHIELD: Target, Test, and Tell" program mitigated the spread of SARS-CoV-2 at a large public university, prevented community transmission, and allowed continuation of in-person classes amidst the pandemic. The program combines epidemiological modelling and surveillance (Target); fast and frequent testing using a novel and FDA Emergency Use Authorized low-cost and scalable saliva-based RT-qPCR assay for SARS-CoV-2 that bypasses RNA extraction, called covidSHIELD (Test); and digital tools that communicate test results, notify of potential exposures, and promote compliance with public health mandates (Tell). These elements were combined with masks, social distancing, and robust education efforts. In Fall 2020, we performed more than 1,000,000 covidSHIELD tests while keeping classrooms, laboratories, and many other university activities open. Generally, our case positivity rates remained less than 0.5%, we prevented transmission from our students to our faculty and staff, and data indicate that we had no spread in our classrooms or research laboratories. During this fall semester, we had zero COVID-19-related hospitalizations or deaths amongst our university community. We also prevented transmission from our university community to the surrounding Champaign County community. Our experience demonstrates that multimodal transmission mitigation programs can enable university communities to achieve such outcomes until widespread vaccination against COVID-19 is achieved, and provides a roadmap for how future pandemics can be addressed.
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@#<p style="text-align: justify;"><strong>Background.</strong> Ultrasound remains to be an ideal imaging tool for the diagnosis of various conditions in the body. However, the cost and unavailability of the commercial acoustic gel continue to hamper the tool's diagnostic value in low-resource communities.</p><p style="text-align: justify;"><strong>Objectives.</strong> The study aims to investigate the feasibility of extracts of common Philippine succulents as ultrasound acoustic gel, based on image quality parameters, organoleptic characteristics, spreadability, pH, and viscosity.</p><p style="text-align: justify;"><strong>Methods.</strong> Aloe Vera, common houseleek, burro's tail, snake plant, echeveria, crown of thorns, panda plant, and jade plant were extracted and filtered before subjecting them for a physical evaluation. The evaluation analyzed the organoleptic characteristics, spreadability, pH, and viscosity of the formulated gels. The commercial acoustic gel was used as the reference gel. Three experienced ultrasonographers blindly evaluated a total of 243 images obtained using the formulated gels based on four image quality parameters.</p><p style="text-align: justify;"><strong>Results.</strong> The formulated gels had optimal appearance, texture, homogeneity, and pH value. However, all of the extracts had a lower viscosity than the commercial reference gel. The extract obtained from the burro's tail exhibited the highest viscosity among the tested extracts. There was no significant difference in the image quality parameters among the commercial and formulated gels.</p><p style="text-align: justify;"><strong>Conclusion.</strong> The extracts obtained from the succulents are feasible as an acoustic gel for ultrasound imaging based on the physical and image quality analyses. The tested plants are readily available and easy to produce compared to commercial acoustic gel.</p>