Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Blood ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38648564

RESUMO

A reciprocal t(3;8) BCL6::MYC fusion is common in large B cell lymphoma (LBCL) with MYC and BCL6 disruption. These pseudo-double hit cases are not adverse, whereas t(3;8) negative MYC/BCL6 lymphoma has an inferior prognosis relative to other MYC-rearranged LBCL.

2.
bioRxiv ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38645084

RESUMO

Background: Anthracyclines such as doxorubicin (Dox) are highly effective anti-tumor agents, but their use is limited by dose-dependent cardiomyopathy and heart failure. Our laboratory previously reported that induction of cytochrome P450 family 1 (Cyp1) enzymes contributes to acute Dox cardiotoxicity in zebrafish and in mice, and that potent Cyp1 inhibitors prevent cardiotoxicity. However, the role of Cyp1 enzymes in chronic Dox cardiomyopathy, as well as the mechanisms underlying cardioprotection associated with Cyp1 inhibition, have not been fully elucidated. Methods: The Cyp1 pathway was evaluated using a small molecule Cyp1 inhibitor in wild-type (WT) mice, or Cyp1-null mice ( Cyp1a1/1a2 -/- , Cyp1b1 -/- , and Cyp1a1/1a2/1b1 -/- ). Low-dose Dox was administered by serial intraperitoneal or intravenous injections, respectively. Expression of Cyp1 isoforms was measured by RT-qPCR, and myocardial tissue was isolated from the left ventricle for RNA sequencing. Cardiac function was evaluated by transthoracic echocardiography. Results: In WT mice, Dox treatment was associated with a decrease in Cyp1a2 and increase in Cyp1b1 expression in the heart and in the liver. Co-treatment of WT mice with Dox and the novel Cyp1 inhibitor YW-130 protected against cardiac dysfunction compared to Dox treatment alone. Cyp1a1/1a2 -/- and Cyp1a1/1a2/1b1 -/- mice were protected from Dox cardiomyopathy compared to WT mice. Male, but not female, Cyp1b1 -/- mice had increased cardiac dysfunction following Dox treatment compared to WT mice. RNA sequencing of myocardial tissue showed upregulation of Fundc1 and downregulation of Ccl21c in Cyp1a1/1a2 -/- mice treated with Dox, implicating changes in mitophagy and chemokine-mediated inflammation as possible mechanisms of Cyp1a-mediated cardioprotection. Conclusions: Taken together, this study highlights the potential therapeutic value of Cyp1a inhibition in mitigating anthracycline cardiomyopathy.

3.
Behav Ecol ; 34(3): 418-425, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37192927

RESUMO

Obtaining nesting material presents an optimal foraging problem, collection of materials incurs a cost in terms of risk of predation and energy spent and individuals must balance these costs with the benefits of using that material in the nest. The hazel dormouse, Muscardinus avellanarius is an endangered British mammal in which both sexes build nests. However, whether material used in their construction follows the predictions of optimal foraging theory is unknown. Here, we analyze the use of nesting materials in forty two breeding nests from six locations in Southwest England. Nests were characterized in terms of which plants were used, the relative amount of each plant, and how far away the nearest source was. We found that dormice exhibit a preference for plants closer to the nest, but that the distance they are prepared to travel depends on the plant species. Dormice traveled further to collect honeysuckle Lonicera periclymenum, oak Quercus robur, and beech Fagus sylvatica than any other plants. Distance did not affect the relative amount used, although the proportion of honeysuckle in nests was highest, and more effort was expended collecting honeysuckle, beech, bramble Rubus fruticosus and oak compared to other plants. Our results suggest that not all aspects of optimal foraging theory apply to nest material collection. However, optimal foraging theory is a useful model to examine nest material collection, providing testable predictions. As found previously honeysuckle is important as a nesting material and its presence should be taken account when assessing suitability of sites for dormice.

4.
Appl Clin Inform ; 14(2): 365-373, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36822226

RESUMO

BACKGROUND: Residents of the Bronx suffer marked health disparities due to socioeconomic and other factors. The coronavirus disease 2019 pandemic worsened these health outcome disparities and health care access disparities, especially with the abrupt transition to online care. OBJECTIVES: This study classified electronic health literacy (EHL) among patients at an urban, academic hospital in the Bronx, and assessed for associations between EHL levels and various demographic characteristics. METHODS: We designed a cross-sectional, observational study in adults 18 years or older presenting to the Montefiore Einstein Center for Cancer Care (MECCC) Department of Radiation Oncology or the Montefiore Department of Medicine in the Bronx. We assessed EHL using the eHealth Literacy Scale (eHEALS) survey, a previously validated tool, and our newly developed eHealth Literacy Objective Scale-Scenario Based (eHeLiOS-SB) tool. RESULTS: A total of 97 patients recruited from the MECCC and Department of Medicine participated in this study. There was a statistically significant association between age and EHL as assessed by both eHEALS and eHeLiOS-SB, with older adults having lower EHL scores. Additionally, a question designed to assess general attitudes toward digital health technologies found that most participants had a positive attitude toward such applications. CONCLUSION: Many patients, especially older adults, may require additional support to effectively navigate telehealth. Further research is warranted to optimize telemedicine strategies in this potentially-marginalized population and ultimately to create telehealth practices accessible to patients of all ages and demographics.


Assuntos
COVID-19 , Letramento em Saúde , Telemedicina , Humanos , Idoso , Estudos Transversais , COVID-19/epidemiologia , Eletrônica , Inquéritos e Questionários , Hospitais , Internet
5.
Sci Adv ; 8(51): eadc9245, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36563141

RESUMO

Anthracyclines such as doxorubicin (Dox) are effective chemotherapies, but their use is limited by cardiac toxicity. We hypothesized that plasma proteomics in women with breast cancer could identify new mechanisms of anthracycline cardiac toxicity. We measured changes in 1317 proteins in anthracycline-treated patients (n = 30) and replicated key findings in a second cohort (n = 31). An increase in the heme-binding protein hemopexin (Hpx) 3 months after anthracycline initiation was associated with cardiac toxicity by echocardiography. To assess the functional role of Hpx, we administered Hpx to wild-type (WT) mice treated with Dox and observed improved cardiac function. Conversely, Hpx-/- mice demonstrated increased Dox cardiac toxicity compared to WT mice. Initial mechanistic studies indicate that Hpx is likely transported to the heart by circulating monocytes/macrophages and that Hpx may mitigate Dox-induced ferroptosis to confer cardioprotection. Together, these observations suggest that Hpx induction represents a compensatory response during Dox treatment.


Assuntos
Antraciclinas , Cardiotoxicidade , Animais , Feminino , Camundongos , Antraciclinas/toxicidade , Antibióticos Antineoplásicos , Cardiotoxicidade/etiologia , Doxorrubicina , Hemopexina/metabolismo , Hemopexina/farmacologia
6.
Parasit Vectors ; 15(1): 407, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329477

RESUMO

BACKGROUND: The canine heartworm Dirofilaria immitis, a filarioid nematode of dogs and other carnivores, is widespread in the USA and the world. Over 20 different mosquito species serve as intermediate hosts of D. immitis, but their contribution to transmission varies according to factors like host feeding patterns, geographic locations and climatic conditions. The yellow fever mosquito, Aedes aegypti, is a competent vector of D. immitis but is often dismissed as a vector of veterinary relevance given its anthropophilic feeding behavior. We evaluated the prevalence of D. immitis in pet dogs along the USA-Mexico border and assessed whether Ae. aegypti in the area are naturally infected with heartworm and are potentially acting as a vector. METHODS: A total of 200 whole blood samples collected from pet dogs in the Lower Rio Grande Valley in south Texas from 2016 to 2019 were included in this study. Canine serum samples for D. immitis were tested using the DiroCHEK® Canine Heartworm Antigen Test Kit pre- and post-immune complex dissociations (ICD) and blood samples were tested using high-resolution melt (HRM) quantitative PCR (qPCR) and a probe-based qPCR. Additionally, mosquito specimens were collected and identified, and Ae. aegypti heads, abdomens and pools were tested using conventional PCR (cPCR) and HRM qPCR. RESULTS: Overall, heartworm prevalence in dogs aged > 6 months was 40.8% (64/157) when the results from all testing modalities were considered. Heartworm antigen was detected in 33.5% and 40.7% of the dogs using DiroCHEK® pre- and post-ICD, respectively. By molecular screening, 20.1% of dogs tested positive with probe-based qPCR, while only one tested positive with HRM qPCR. Of the Ae. aegypti abdomens from blood-fed Ae. aeygpti tested, 20 (21.7%) from mosquitoes that fed on dogs and four (7%) from those that fed on humans tested positive for heartworm. Among Ae. aegypti heads from blood-fed Ae. aeygpti, two (1.1%) were positive based on cPCR and four (2.5%) were positive based on HRM qPCR. No D. immitis DNA was detected in the 208 pools of whole bodies (358 individuals) of Ae. aegypti gravid females. CONCLUSIONS: Our study highlights a high prevalence of heartworm in dogs in south Texas and provides evidence that Ae. aegypti could be contributing to heartworm transmission in canine populations in this region.


Assuntos
Aedes , Dirofilaria immitis , Dirofilariose , Doenças do Cão , Humanos , Feminino , Cães , Animais , Dirofilaria immitis/genética , Dirofilariose/epidemiologia , Prevalência , Texas/epidemiologia , Mosquitos Vetores , Doenças do Cão/epidemiologia
7.
Support Care Cancer ; 30(11): 9587-9596, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36136246

RESUMO

PURPOSE: Immune checkpoint inhibitors (ICIs) and targeted therapy (TT) have improved the survival of people with metastatic melanoma. We assessed the feasibility, acceptability, and utility of a novel model of nurse-led, telehealth-delivered survivorship care (MELCARE) for this survivor group. METHODS: People ≥ 18 years diagnosed with unresectable stage III or stage IV melanoma who were ≥ 6 months post initiation of ICI/TT with a radiological response suggestive of a long-term response to ICI/TT were recruited from a specialist melanoma centre in Australia. All participants received MELCARE, a nurse-led survivorship program involving two telehealth consultations 3 months apart, needs assessment using the Distress Thermometer (DT) and Problem List, and creation of a survivorship care plan. Feasibility, acceptability, and utility were assessed using rates of consent and study completion, time taken to complete each component of MELCARE, the Acceptability of Intervention Measure (AIM), and a customised utility survey. RESULTS: 31/54 (57%) people consented. Participants were male (21, 68%), with a median age of 67 (range: 46-82). Eleven (35%) were receiving/had received ipilimumab and nivolumab and 27 (87%) had ceased treatment. Feasibility was demonstrated with 97% completing MELCARE. Utility was demonstrated on a customised survey and supported by a reduction in the mean DT score (initial: 5.6, SD: 2.9; follow-up: 1.5, SD: 1.2). Acceptability was demonstrated on 3/4 AIM items. CONCLUSION: MELCARE was feasible and acceptable with high levels of utility. However, the consent rate was 57% indicating some people do not require support. Future studies should consider MELCARE's optimal timing, resourcing, and cost-effectiveness.


Assuntos
Melanoma , Segunda Neoplasia Primária , Masculino , Humanos , Feminino , Sobrevivência , Estudos de Viabilidade , Papel do Profissional de Enfermagem , Melanoma/tratamento farmacológico , Inquéritos e Questionários
8.
AACE Clin Case Rep ; 8(4): 163-165, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35959080

RESUMO

Objective: Emphysematous cystitis (EC) is a rare urinary tract infection (UTI) typically associated with severe diabetes in older women. We present a unique case of this gas-forming infection in a man with type 2 diabetes mellitus (T2DM) treated with empagliflozin. To the best of our knowledge, this is the first case report of EC associated with the use of a sodium-glucose cotransporter 2 inhibitor (SGLT2i). Case Report: A 62-year-old man with T2DM treated with an SGLT2i developed EC. His moderately controlled T2DM was treated for over 20 years with metformin, saxagliptin/metformin, and pioglitazone to which empagliflozin was added due to his consistently elevated hemoglobin A1c level, slightly reduced estimated glomerular filtration rate, and proteinuria. Four months after initiation of the SGLT2i, he reported lower urinary tract symptoms and was found to have EC radiographically. His urine cultures were positive for Klebsiella pneumonia and was found to have asymptomatic urinary retention. He was treated conservatively, and his outcome was favorable. Discussion: EC is commonly seen in patients with diabetes mellitus, and symptoms range from asymptomatic to severe sepsis. Most urine cultures grow Escherichia coli and K. pneumonia. The association of increased UTIs in susceptible patients with T2DM with the use of SGLT2i is yet to be determined. Most cases of EC are diagnosed radiographically and treated conservatively, although some cases require surgical intervention. Conclusion: Initially, our patient was considered a good candidate for treatment with an SGLT2i. The subsequent development of EC precluded its further use. The role of SGLT2i in patients with T2DM susceptible to UTI is controversial.

9.
Curr Cardiol Rep ; 23(3): 17, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33537861

RESUMO

PURPOSE OF REVIEW: 5-fluorouracil (5-FU) is one of the most common causes of cardiotoxicity associated with chemotherapy. The manifestations of 5-FU cardiotoxicity are diverse, and there are no established clinical guidelines addressing the diagnosis and management of this condition. Here we summarize the mechanistic and clinical data available to guide clinicians in caring for patients with suspected 5-FU cardiotoxicity. RECENT FINDINGS: The decision to resume 5-FU treatment in patients with suspected cardiovascular toxicity remains challenging. Testing for predisposing genetic variants may be helpful, particularly in patients with other signs of 5-FU toxicity. Uridine triacetate is a recently approved antidote that can improve clinical outcomes in patients with life-threatening fluoropyrimidine cardiotoxicity. 5-FU cardiotoxicity remains poorly understood, with limited mechanistic or prospective clinical trial data available to define risk factors or effective management strategies. Risk stratification and therapeutic decisions should be individualized, based on the risk-benefit ratio of continuing 5-FU therapy for each patient.


Assuntos
Miocardite , Cardiotoxicidade/etiologia , Morte Súbita , Fluoruracila/efeitos adversos , Humanos , Estudos Prospectivos
10.
J Cardiovasc Dev Dis ; 8(2)2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33499052

RESUMO

PURPOSE OF REVIEW: Both traditional and novel cancer therapies can cause cardiovascular toxicity in patients. In vivo models integrating both cardiovascular and cancer phenotypes allow for the study of on- and off-target mechanisms of toxicity arising from these agents. The zebrafish is the optimal whole organism model to screen for cardiotoxicity in a high throughput manner, while simultaneously assessing the role of cardiotoxicity pathways on the cancer therapy's antitumor effect. Here we highlight established zebrafish models of human cardiovascular disease and cancer, the unique advantages of zebrafish to study mechanisms of cancer therapy-associated cardiovascular toxicity, and finally, important limitations to consider when using the zebrafish to study toxicity. RECENT FINDINGS: Cancer therapy-associated cardiovascular toxicities range from cardiomyopathy with traditional agents to arrhythmias and thrombotic complications associated with newer targeted therapies. The zebrafish can be used to identify novel therapeutic strategies that selectively protect the heart from cancer therapy without affecting antitumor activity. Advances in genome editing technology have enabled the creation of several transgenic zebrafish lines valuable to the study of cardiovascular and cancer pathophysiology. SUMMARY: The high degree of genetic conservation between zebrafish and humans, as well as the ability to recapitulate cardiotoxic phenotypes observed in patients with cancer, make the zebrafish an effective model to study cancer therapy-associated cardiovascular toxicity. Though this model provides several key benefits over existing in vitro and in vivo models, limitations of the zebrafish model include the early developmental stage required for most high-throughput applications.

11.
Biol Lett ; 16(10): 20200443, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33108983

RESUMO

Animal contest theory assumes individuals to possess accurate information about their own fighting ability or resource-holding potential (RHP) and, under some models, that of their opponent. However, owing to the difficulty of disentangling perceived and actual RHP in animals, how accurately individuals are able to assess RHP remains relatively unknown. Furthermore, it is not just individuals within a fight that evaluate RHP. Third-party observers evaluate the fight performance of conspecifics in order to make behavioural decisions. In human combat sports, when fights remain unresolved at the end of the allotted time, bystanders take a more active role, with judges assigning victory based on their assessment of each fighter's performance. Here, we use fight data from mixed martial arts in order to investigate whether perceived fighting performance (judges' decisions) and actual fighting success (fights ending in knockout or submission) are based on the same performance traits, specifically striking skill and vigour. Our results indicate that both performance traits are important for victory, but that vigour is more important for fights resolved via decision, even though the effect of vigour is enhanced by skill. These results suggest that while similar traits are important for fighting success across the board, vigour is overvalued in judges' perceptions of RHP.


Assuntos
Esportes , Animais , Humanos
12.
Anim Behav ; 167: 111-118, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32952200

RESUMO

Understanding the determinants of fighting ability (or resource-holding potential, RHP) is key to elucidating the evolution of aggressive behaviour, as current tests of contest theory rely on realistic proxies for overall RHP. Traditionally, RHP is considered equivalent to body size but it is increasingly clear that a wider range of morphological and physiological traits contribute to fighting ability. In situations analogous to contests, such as courtship displays in animals and competitive sport in humans, the role of skill has long been appreciated but this component has been neglected in analyses of animal fights. Here, we investigated two spatial components of skill, accuracy and precision, during shell fights in hermit crabs, where an attacker repeatedly strikes (raps) its shell against that of a defender. By analysing the points of impact of these strikes, we found that attackers that rapped with coarse-scale accuracy were more likely to win the fight, indicating that the ability to target a 'sweet spot' on the defender's shell is an important determinant of contest success. Furthermore, we found that this element of skill correlated with temporal performance (vigour). Taken together these results show that spatial skill is an RHP component. Moreover, in contrast to the traditional assumption that fighting ability is equivalent to body size, RHP is actually underpinned by a suite of interlinked traits including performance capacities, morphology and skill.

13.
J Pharm Sci ; 109(11): 3480-3489, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32791073

RESUMO

Diverging physicochemical properties of HIV drug combinations are challenging to formulate as a single dosage form. We have found that 2-to-4 hydrophilic and hydrophobic HIV drugs in combination can be stabilized with lipid excipients under a controlled solvent removal process to form a novel pharmaceutical powder distinct from typical amorphous material. This discovery has enabled production of a drug combination nanoparticle (DcNP) powder composed of 3 HIV drugs-water-insoluble lopinavir (LogP = 4.7) and ritonavir (LogP = 5.6) and water-soluble tenofovir (LogP = -1.6). DcNP powder, exhibiting repeating units of multi-drug-motifs (referred to as MDM), is made by dissolving all constituents in ethanolic solution, followed by controlled solvent removal. The DcNP powder intersperses chemically diverse drug molecules with lipid excipients to form repeating MDM units. The proposed MDM structure is consistent with data collected with X-ray diffraction, differential calorimetry, and time-of-flight secondary ion mass spectrometry. The successful assembly of chemically diverse drugs in MDM structure is likely due to a novel process of making drug combination powders. The method described here has successfully extended to formulating other clinically prescribed antiviral drug combinations, and thus may serve as a platform technology for developing drug combination nanoparticles for treating a wide range of chronic diseases.


Assuntos
Excipientes , Ritonavir , Antivirais , Varredura Diferencial de Calorimetria , Química Farmacêutica , Combinação de Medicamentos , Lopinavir , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Pós , Solventes , Tenofovir , Difração de Raios X
14.
Behav Ecol ; 31(2): 540-547, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210526

RESUMO

Theoretical models of animal contests such as the Hawk-Dove game predict that variation in fighting behavior will persist due to mixed evolutionarily stable strategies (ESS) under certain conditions. However, the genetic basis for this variation is poorly understood and a mixed ESS for fighting can be interpreted in more than one way. Specifically, we do not know whether variation in aggression within a population arises from among-individual differences in fixed strategy (determined by an individual's genotype-direct genetic effects [DGEs]), or from within-individual variation in strategy across contests. Furthermore, as suggested by developments of the original Hawk-Dove model, within-individual variation in strategy may be dependent on the phenotype and thus genotype of the opponent (indirect genetic effects-IGEs). Here we test for the effect of DGEs and IGEs during fights in the beadlet sea anemone Actinia equina. By exploiting the unusual reproductive system of sea anemones, combined with new molecular data, we investigate the role of both additive (DGE + IGE) and non-additive (DGE × IGE) genetic effects on fighting parameters, the latter of which have been hypothesized but never tested for explicitly. We find evidence for heritable variation in fighting ability and that fight duration increases with relatedness. Fighting success is influenced additively by DGEs and IGEs but we found no evidence for non-additive IGEs. These results indicate that variation in fighting behavior is driven by additive indirect genetic effects (DGE + IGE), and support a core assumption of contest theory that strategies are fixed by DGEs.

15.
Chembiochem ; 21(13): 1905-1910, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32003101

RESUMO

Doxorubicin is a highly effective chemotherapy agent used to treat many common malignancies. However, its use is limited by cardiotoxicity, and cumulative doses exponentially increase the risk of heart failure. To identify novel heart failure treatment targets, a zebrafish model of doxorubicin-induced cardiomyopathy was previously established for small-molecule screening. Using this model, several small molecules that prevent doxorubicin-induced cardiotoxicity both in zebrafish and in mouse models have previously been identified. In this study, exploration of doxorubicin cardiotoxicity is expanded by screening 2271 small molecules from a proprietary, target-annotated tool compound collection. It is found that 120 small molecules can prevent doxorubicin-induced cardiotoxicity, including 7 highly effective compounds. Of these, all seven exhibited inhibitory activity towards cytochrome P450 family 1 (CYP1). These results are consistent with previous findings, in which visnagin, a CYP1 inhibitor, also prevents doxorubicin-induced cardiotoxicity. Importantly, genetic mutation of cyp1a protected zebrafish against doxorubicin-induced cardiotoxicity phenotypes. Together, these results provide strong evidence that CYP1 is an important contributor to doxorubicin-induced cardiotoxicity and highlight the CYP1 pathway as a candidate therapeutic target for clinical cardioprotection.


Assuntos
Cardiomiopatias/prevenção & controle , Família 1 do Citocromo P450/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Animais Geneticamente Modificados , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/patologia , Família 1 do Citocromo P450/antagonistas & inibidores , Família 1 do Citocromo P450/genética , Modelos Animais de Doenças , Doxorrubicina/toxicidade , Insuficiência Cardíaca , Mutagênese , Fenótipo , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/metabolismo , Bibliotecas de Moléculas Pequenas/uso terapêutico , Relação Estrutura-Atividade , Peixe-Zebra , Proteínas de Peixe-Zebra/antagonistas & inibidores , Proteínas de Peixe-Zebra/genética
16.
J Pharm Sci ; 109(5): 1789-1801, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32006525

RESUMO

TLC-ART101 is a long-acting triple-HIV drug combination of lopinavir-ritonavir-tenofovir in one nanosuspension intended for subcutaneous injection. After a single TLC-ART 101 administration in nonhuman primates, drug concentrations in both plasma and HIV-target lymph node mononuclear cells were sustained for 2 weeks. Nevertheless, the mechanisms leading to the targeted long-acting pharmacokinetics remain elusive. Therefore, an intravenous study of TLC-ART 101 in nonhuman primates was conducted to elucidate the degree of association of drugs in vivo, estimate subcutaneous bioavailability, and refine a mechanism-based pharmacokinetic (MBPK2) model. The MBPK2 model considers TLC-ART 101 systemic drug clearances, nanoparticle-associated/dissociated species, more detailed mechanisms of lymphatic first-pass retention of associated-drugs after subcutaneous administrations, and the prediction of drug concentration time-courses in lymph node mononuclear cells. For all 3 drugs, we found a high association with the nanoparticles in plasma (>87% lopinavir-ritonavir, 97% tenofovir), and an incomplete subcutaneous bioavailability (<29% lopinavir-ritonavir, 85% tenofovir). As hypothesized by the MBPK2 model, the incomplete SC bioavailability observed is due to sequestration into a lymphatic node depot after subcutaneous absorption (unlike most intramuscular nanodrug products having near-to-injection depots), which contributes to long-acting profiles detected in plasma and target cells. This combined experimental and modeling approach may be applicable for the clinical development of other long-acting drug-combination injectables.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Preparações Farmacêuticas , Animais , Fármacos Anti-HIV/uso terapêutico , Combinação de Medicamentos , Infecções por HIV/tratamento farmacológico , Lopinavir , Ritonavir
17.
J Exp Biol ; 221(Pt 19)2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30115671

RESUMO

An individual's performance during a fight is influenced by a combination of their capacity and willingness to compete. While willingness to fight is known to be determined by both intrinsic and extrinsic drivers, an individual's capacity to fight is generally thought of as solely intrinsic, being driven by a host of physiological factors. However, evidence indicates that variation in fighting ability can also be generated through exposure to different environmental conditions. Environmental contributions to fighting ability may be particularly important for animals living in spatially and temporally heterogeneous habitats, in which fights can occur between rivals recently exposed to different environmental conditions. The rapidly changing environment experienced within intertidal zones, for example, means that seawater parameters, including dissolved oxygen content and temperature, can vary across small spatial and temporal scales. Here, we investigated the relative importance of these extrinsic contributions to fighting ability and resource value on contest dynamics in the beadlet sea anemone Actinia equina We manipulated the extrinsic fighting ability of both opponents (through dissolved oxygen concentration prior to fights) and resource value (through seawater flow rate during the fight). Our results indicate that the extrinsic fighting ability of both opponents can interact with resource value to drive escalation patterns and that extrinsic drivers can be more important in determining contest dynamics than the intrinsic traits commonly studied. Our study highlights the need to combine data on intrinsic state and extrinsic conditions in order to gain a more holistic view of the factors driving contest behaviour.


Assuntos
Oxigênio/análise , Anêmonas-do-Mar/fisiologia , Água do Mar/química , Movimentos da Água , Agressão , Animais , Meio Ambiente
18.
Integr Comp Biol ; 58(6): 1055-1063, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30010939

RESUMO

Animals utilize an incredible array of traits for offence and defence during conflict. These traits range from exaggerated morphological structures such as the antlers of stags and the horns of beetles, to an arsenal of noxious chemicals emitted, secreted, and injected. However, the breadth of these traits appears to be underappreciated in our current thinking about aggression in animals. Use of the term "weapon" in the current literature is largely restricted to studies of conspicuous morphological structures used by males during contests over access to females, and as a result, our understanding of other types of weapons is limited. In this article, I explore the diversity of traits utilized by animals to manipulate and control the behavior of other individuals in a number of agonistic contexts, with the aim to encourage a reappraisal of the way in which behavioral and evolutionary biologists view animal weapons. I discuss the advantages of including this broader range of traits in studies of animal weaponry and explore the unifying features that distinguish animal weapons from other traits.


Assuntos
Agressão , Evolução Biológica , Invertebrados/fisiologia , Vertebrados/fisiologia , Animais , Comportamento Animal , Feminino , Invertebrados/anatomia & histologia , Masculino , Caracteres Sexuais , Comportamento Sexual Animal , Vertebrados/anatomia & histologia , Armas
19.
J Chem Phys ; 148(22): 222825, 2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29907018

RESUMO

Surface-specific nonlinear vibrational spectroscopy, combined with bulk solution measurements and imaging, is used to study the surface conditions during the growth of E. coli. As a result of the silica high surface charge density, the water structure at the silica-aqueous interface is known to be especially sensitive to pH and ionic strength, and surface concentration profiles develop that can be appreciably different from the bulk solution conditions. We illustrate that, in the presence of growing cells, a unique surface micro-environment is established as a result of metabolites accumulating on the silica surface. Even in the subsequent absence of the cells, this surface layer works to reduce the interfacial ionic strength as revealed by the enhanced signal from surface water molecules. In the presence of growing cells, an additional boost in surface water signal is attributed to a local pH that is higher than that of the bulk solution.


Assuntos
Escherichia coli/crescimento & desenvolvimento , Água/metabolismo , Escherichia coli/citologia , Escherichia coli/metabolismo , Concentração de Íons de Hidrogênio , Íons/química , Íons/metabolismo , Dióxido de Silício/química , Dióxido de Silício/metabolismo , Espectrofotometria Infravermelho , Propriedades de Superfície , Água/química
20.
Crit Care Nurs Q ; 41(3): 297-301, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29851679

RESUMO

The health care team must be able to mobilize bariatric patients efficiently and safely. It is challenging to find the proper equipment of sufficient variety to meet the need. Patients can feel self-conscious when staff are struggling to provide care, and staff can be injured when trying to mobilize patients without the proper equipment. This can result in feelings of humiliation for the patient and frustration for staff. Furthermore, staff often experience compassion fatigue when dealing with their frustration around this. This bariatric surgery unit experienced these issues with mobilization of larger patients and participated in the development of a Safe Patient Handling and Mobility program in an effort to gain understanding of the necessary equipment and how to implement such a program. The purpose of this article is to describe the successful implementation of a Safe Patient Handling and Mobility program to reduce staff injury and frustration and to improve the patient experience on a bariatric unit.


Assuntos
Cirurgia Bariátrica/enfermagem , Deambulação Precoce , Movimentação e Reposicionamento de Pacientes/métodos , Segurança do Paciente , Humanos , Movimentação e Reposicionamento de Pacientes/instrumentação , Equipe de Assistência ao Paciente/estatística & dados numéricos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...