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1.
Sci Adv ; 6(5): eaay7934, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32064354

RESUMO

We demonstrate direct eddy covariance (EC) observations of methane (CH4) fluxes between the sea and atmosphere from an icebreaker in the eastern Arctic Ocean. EC-derived CH4 emissions averaged 4.58, 1.74, and 0.14 mg m-2 day-1 in the Laptev, East Siberian, and Chukchi seas, respectively, corresponding to annual sea-wide fluxes of 0.83, 0.62, and 0.03 Tg year-1. These EC results answer concerns that previous diffusive emission estimates, which excluded bubbling, may underestimate total emissions. We assert that bubbling dominates sea-air CH4 fluxes in only small constrained areas: A ~100-m2 area of the East Siberian Sea showed sea-air CH4 fluxes exceeding 600 mg m-2 day-1; in a similarly sized area of the Laptev Sea, peak CH4 fluxes were ~170 mg m-2 day-1. Calculating additional emissions below the noise level of our EC system suggests total ESAS CH4 emissions of 3.02 Tg year-1, closely matching an earlier diffusive emission estimate of 2.9 Tg year-1.

2.
Surg Endosc ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399944

RESUMO

BACKGROUND: Cameron lesions (CL) are common complications of large hiatal hernia (HH) disease and are known to result in chronic blood loss with resultant microcytic anemia. There is support in the literature that repair of HH may lead to resolution of CL and restore normal hemoglobin levels. This study aimed to determine the impact of elective HH repair on resolution of anemia and the quality of life (QOL) in patients with CL. METHOD: A single-institution, retrospective review analyzed all patients with history of CL or anemia (hemoglobin < 12.0 gm/dl in women, < 13.5 gm/dl in men) who underwent HH repair from January 2012 to May 2019. Four validated surveys were used to assess QOL: Reflux Symptom Index (RSI), gastroesophageal reflux disease health-related QOL (GERD-HRQL), laryngopharyngeal reflux health-related QOL (LPR-HRQL), and QOL and swallowing disorders (SWAL) survey. History of iron supplements and perioperative hemoglobin were also noted. RESULT: Ninety-six patients were included in this study. The mean age was 67.4 ± 10.8 years and 79% of patients were female. CL were endoscopically identified in 61.5% of patients preoperatively, and the rest of the patients experienced anemia of undiagnosed origin but had a high suspicion for CL. Mean follow-up after HH repair was 17.3 months (range, 1 month-5 years). Mean preoperative hemoglobin was 11.01 ± 2.9 gm/dl and 13.23 ± 1.6 gm/dl postoperatively (p < 0.01). Forty-two (73.7%) patients had resolution of anemia during follow-up and 94.5% stopped supplemental oral iron. Finally, QOL scores significantly improved after surgical intervention: RSI (63%), GERD-HRQL (77%), LPR-HRQOL (72%), and SWAL (13%). CONCLUSION: Elective HH repair in patients with chronic anemia secondary to CL may potentially resolve CL and anemia and contribute to significant QOL improvements. Future studies will prospectively assess the resolution of CL with biochemical and endoscopic follow-up to confirm the preliminary findings of our analysis.

3.
J Am Pharm Assoc (2003) ; 59(2S): S21-S24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30448025

RESUMO

OBJECTIVE: To describe opportunities for pharmacists to use mobile messaging and real-time monitoring to engage with patients taking long-term medications. SUMMARY: The proliferation of mobile phone use across the United States has been met with increased application of these devices by the medical community. However, beyond simple text messages and app-based functions, use of these devices by pharmacies and pharmacists has not been leveraged to improve patient outcomes, such as medication adherence. Resources now exist that can facilitate more advanced mobile communication between patients and pharmacists, which can be managed and informed by data available in most pharmacies. Such tailored messaging can be personalized further by being reactive to patient behavior using real-time medication use monitoring tools, facilitating low-cost, high-reach interventions for patients in need of ongoing guidance. CONCLUSION: Mechanisms now exist for pharmacies to engage patients more proactively with their prescribed therapy using mobile communication and devices. By facilitating such engagement, pharmacists can remain connected with patients throughout their care, better interpret their needs, navigate adherence-related issues, and more holistically counsel patients based on observed behaviors. Community pharmacy leadership should pursue the use of these advanced mobile messaging techniques as another tool in their arsenal to improve patient outcomes.

5.
Nature ; 525(7568): 234-8, 2015 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-26354482

RESUMO

The amount of ice present in clouds can affect cloud lifetime, precipitation and radiative properties. The formation of ice in clouds is facilitated by the presence of airborne ice-nucleating particles. Sea spray is one of the major global sources of atmospheric particles, but it is unclear to what extent these particles are capable of nucleating ice. Sea-spray aerosol contains large amounts of organic material that is ejected into the atmosphere during bubble bursting at the organically enriched sea-air interface or sea surface microlayer. Here we show that organic material in the sea surface microlayer nucleates ice under conditions relevant for mixed-phase cloud and high-altitude ice cloud formation. The ice-nucleating material is probably biogenic and less than approximately 0.2 micrometres in size. We find that exudates separated from cells of the marine diatom Thalassiosira pseudonana nucleate ice, and propose that organic material associated with phytoplankton cell exudates is a likely candidate for the observed ice-nucleating ability of the microlayer samples. Global model simulations of marine organic aerosol, in combination with our measurements, suggest that marine organic material may be an important source of ice-nucleating particles in remote marine environments such as the Southern Ocean, North Pacific Ocean and North Atlantic Ocean.


Assuntos
Atmosfera/química , Gelo , Aerossóis/síntese química , Aerossóis/química , Ar , Organismos Aquáticos/química , Regiões Árticas , Diatomáceas/química , Congelamento , Compostos Orgânicos/análise , Compostos Orgânicos/química , Fitoplâncton/química , Água do Mar/química
6.
Clin Exp Pharmacol ; 4(1): 142, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25105064

RESUMO

Intradermally injected capsaicin has been used extensively both as a human pain model and to assess analgesic efficacy. Factors such as dose, formulation, route, and site are known to affect its sensitivity. We determined whether potency and stability of capsaicin solutions were further sources of variability when following strict manufacturing guidelines. Capsaicin solution (1.0 mg/mL) was prepared according to Current Good Manufacturing Practice (cGMP) guidelines and aseptically filled into sterile amber borosilicate vials and stored at 5°C, 25°C, and 30°C. All samples were analyzed at one, three, six, and twelve months. Chemical stability was determined using HPLC and physical stability was evaluated by visual inspection of color changes, clarity, particulate matter, and product/ container closure abnormalities during each sampling time. Capsaicin intradermal injection was found to be sterile and retained 95% of the initial concentration for at least one year, regardless of studied storage temperatures (P<0.0001). Visual inspection indicated no changes in color, clarity, particulate matter, and product/ container closure abnormalities in all samples. These data show that capsaicin solutions (1.0 mg/mL) maintain their potency and stability over one year when manufactured according to cGMP guidelines. These results suggest that in clinical trials manufacturing of capsaicin solutions is recommended over extemporaneous compounding.

7.
J Neurosci ; 33(9): 4151-64, 2013 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-23447623

RESUMO

Selective control of receptor trafficking provides a mechanism for remodeling the receptor composition of excitatory synapses, and thus supports synaptic transmission, plasticity, and development. GluN3A (formerly NR3A) is a nonconventional member of the NMDA receptor (NMDAR) subunit family, which endows NMDAR channels with low calcium permeability and reduced magnesium sensitivity compared with NMDARs comprising only GluN1 and GluN2 subunits. Because of these special properties, GluN3A subunits act as a molecular brake to limit the plasticity and maturation of excitatory synapses, pointing toward GluN3A removal as a critical step in the development of neuronal circuitry. However, the molecular signals mediating GluN3A endocytic removal remain unclear. Here we define a novel endocytic motif (YWL), which is located within the cytoplasmic C-terminal tail of GluN3A and mediates its binding to the clathrin adaptor AP2. Alanine mutations within the GluN3A endocytic motif inhibited clathrin-dependent internalization and led to accumulation of GluN3A-containing NMDARs at the cell surface, whereas mimicking phosphorylation of the tyrosine residue promoted internalization and reduced cell-surface expression as shown by immunocytochemical and electrophysiological approaches in recombinant systems and rat neurons in primary culture. We further demonstrate that the tyrosine residue is phosphorylated by Src family kinases, and that Src-activation limits surface GluN3A expression in neurons. Together, our results identify a new molecular signal for GluN3A internalization that couples the functional surface expression of GluN3A-containing receptors to the phosphorylation state of GluN3A subunits, and provides a molecular framework for the regulation of NMDAR subunit composition with implications for synaptic plasticity and neurodevelopment.


Assuntos
Endocitose/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/química , Receptores de N-Metil-D-Aspartato/metabolismo , Tirosina/metabolismo , Trifosfato de Adenosina/farmacocinética , Motivos de Aminoácidos/efeitos dos fármacos , Motivos de Aminoácidos/genética , Análise de Variância , Animais , Biofísica , Biotinilação , Células Cultivadas , Córtex Cerebral/citologia , Chlorocebus aethiops , Clatrina/farmacologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Estimulação Elétrica , Embrião de Mamíferos , Endocitose/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Ácido Glutâmico/farmacologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hipocampo/citologia , Humanos , Imunoprecipitação , Mutagênese/fisiologia , Mutação/fisiologia , Neurônios/efeitos dos fármacos , Neurotransmissores/farmacologia , Técnicas de Patch-Clamp , Isótopos de Fósforo/farmacocinética , Fosforilação/efeitos dos fármacos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/genética , Conformação Proteica , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Receptores de N-Metil-D-Aspartato/genética , Transfecção , Transferrina/metabolismo
8.
J Biol Chem ; 286(8): 6697-706, 2011 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-21156788

RESUMO

GluA1 (formerly GluR1) AMPA receptor subunit phosphorylation at Ser-831 is an early biochemical marker for long-term potentiation and learning. This site is a substrate for Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) and protein kinase C (PKC). By directing PKC to GluA1, A-kinase anchoring protein 79 (AKAP79) facilitates Ser-831 phosphorylation and makes PKC a more potent regulator of GluA1 than CaMKII. PKC and CaM bind to residues 31-52 of AKAP79 in a competitive manner. Here, we demonstrate that common CaMKII inhibitors alter PKC and CaM interactions with AKAP79(31-52). Most notably, the classical CaMKII inhibitors KN-93 and KN-62 potently enhanced the association of CaM to AKAP79(31-52) in the absence (apoCaM) but not the presence of Ca(2+). In contrast, apoCaM association to AKAP79(31-52) was unaffected by the control compound KN-92 or a mechanistically distinct CaMKII inhibitor (CaMKIINtide). In vitro studies demonstrated that KN-62 and KN-93, but not the other compounds, led to apoCaM-dependent displacement of PKC from AKAP79(31-52). In the absence of CaMKII activation, complementary cellular studies revealed that KN-62 and KN-93, but not KN-92 or CaMKIINtide, inhibited PKC-mediated phosphorylation of GluA1 in hippocampal neurons as well as AKAP79-dependent PKC-mediated augmentation of recombinant GluA1 currents. Buffering cellular CaM attenuated the ability of KN-62 and KN-93 to inhibit AKAP79-anchored PKC regulation of GluA1. Therefore, by favoring apoCaM binding to AKAP79, KN-62 and KN-93 derail the ability of AKAP79 to efficiently recruit PKC for regulation of GluA1. Thus, AKAP79 endows PKC with a pharmacological profile that overlaps with CaMKII.


Assuntos
Proteínas de Ancoragem à Quinase A/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase C/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Receptores de AMPA/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas de Ancoragem à Quinase A/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Ativação Enzimática/efeitos dos fármacos , Células HEK293 , Hipocampo/metabolismo , Humanos , Neurônios/metabolismo , Fosforilação/efeitos dos fármacos , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/genética , Receptores de AMPA/genética
10.
Perspect Health Inf Manag ; 6: 6, 2009 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-19471646

RESUMO

With the current national emphasis on translational research, data-exchange systems that can bridge the basic and clinical sciences are vital. To meet this challenge, we have developed Slim-Prim, an integrated data system (IDS) for collecting, processing, archiving, and distributing basic and clinical research data. Slim-Prim is accessed via user-friendly Web-based applications, thus increasing data accessibility and eliminating the security risks inherent with office or laboratory servers. Slim-Prim serves as a laboratory management interface and archival data repository for institutional projects. Importantly, multiple levels of controlled access allow HIPAA-compliant sharing of de-identified information to facilitate data sharing and analysis across research domains; thus Slim-Prim encourages collaboration between researchers and clinicians, an essential factor in the development of translational research. Slim-Prim is an example of utilizing an IDS to improve organizational efficiency and to bridge the gap between laboratory discovery and practice.


Assuntos
Difusão de Inovações , Aplicações da Informática Médica , Ensaios Clínicos como Assunto , Bases de Dados Factuais , Humanos , Armazenamento e Recuperação da Informação/métodos , Internet , Sistemas Computadorizados de Registros Médicos/organização & administração
11.
Clin Transl Sci ; 2(3): 238-41, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20443897

RESUMO

With current national emphasis on translational research, data exchange systems are needed that bridge basic science and clinical research. To meet this challenge, an electronic system was developed by the Biomedical Informatics Unit (BMIU) of the University of Tennessee Clinical Translation Science Institute (UT CTSI). This integrated data system collects, processes, archives, and distributes basic, clinical, and translational research data. The system provides information via web-based applications in a secure and Health Insurance Portability and Accountability Act (HIPAA)-compliant manner to facilitate data sharing and analysis across domains. The system is currently in use by a number of studies and has proven to be an effective tool for data collection and processing in clinical studies.


Assuntos
Sistemas de Informação em Laboratório Clínico , Prática Profissional , Sistemas de Gerenciamento de Base de Dados , Humanos , Sistemas Computadorizados de Registros Médicos , Seleção de Pacientes , Inquéritos e Questionários , Bancos de Tecidos
13.
J Neurosci ; 25(21): 5109-16, 2005 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-15917451

RESUMO

Transient receptor potential (TRP) channels detect diverse sensory stimuli, including alterations in osmolarity. However, a molecular detector of noxious hypertonic stimuli has not yet been identified. We show here that acute pain-related behavior evoked by elevated ionic strength is abolished in TRP vanilloid subtype 1 (TRPV1)-null mice and inhibited by iodoresiniferatoxin, a potent TRPV1 antagonist. Electrophysiological recordings demonstrate a novel form of ion channel modulation by which extracellular Na+, Mg2+, and Ca2+ ions sensitize and activate the capsaicin receptor, TRPV1. At room temperature, increasing extracellular Mg2+ (from 1 to 5 mM) or Na+ (+50 mM) increased ligand-activated currents up to fourfold, and 10 mM Mg2+ reduced the EC50 for activation by capsaicin from 890 to 450 nM. Moreover, concentrations of divalent cations >10 mM directly gate the receptor. These effects occur via electrostatic interactions with two glutamates (E600 and E648) formerly identified as proton-binding residues. Furthermore, phospholipase C-mediated signaling enhances the effects of cations, and physiological concentrations of cations contribute to the bradykinin-evoked activation of TRPV1 and the sensitization of the receptor to heat. Thus, the modulation of TRPV1 by cationic strength may contribute to inflammatory pain signaling.


Assuntos
Cátions/farmacologia , Espaço Extracelular/metabolismo , Dor/fisiopatologia , Transdução de Sinais/fisiologia , Canais de Cátion TRPV/fisiologia , Trifosfato de Adenosina/farmacologia , Aminobutiratos , Animais , Ácidos Araquidônicos/farmacologia , Comportamento Animal/fisiologia , Bradicinina , Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio , Capsaicina/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Interações Medicamentosas , Estimulação Elétrica/métodos , Endocanabinoides , Espaço Extracelular/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Sulfato de Magnésio/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Potenciais da Membrana/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microinjeções , Modelos Biológicos , Mutagênese , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Gânglio Nodoso/citologia , Oócitos , Dor/induzido quimicamente , Dor/genética , Técnicas de Patch-Clamp/métodos , Dibutirato de 12,13-Forbol/farmacologia , Alcamidas Poli-Insaturadas , Proteína Quinase C , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Canais de Cátion TRPV/deficiência , Temperatura , Fatores de Tempo , Transfecção/métodos
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