RESUMEN
Doping, or incremental substitution of one element for another, is an effective way to tailor a compound's structure as well as its physical and chemical properties. Herein, we replaced up to 30% of Ni with Co in members of the family of layered LiNiB compounds, stabilizing the high-temperature polymorph of LiNiB while the room-temperature polymorph does not form. By studying this layered boride with in situ high-temperature powder diffraction, we obtained a distorted variant of LiNi0.7Co0.3B featuring a perfect interlayer placement of [Ni0.7Co0.3B] layers on top of each otherâa structural motif not seen before in other borides. Because of the Co doping, LiNi0.7Co0.3B can undergo a nearly complete topochemical Li deintercalation under ambient conditions, resulting in a metastable boride with the formula Li0.04Ni0.7Co0.3B. Heating of Li0.04Ni0.7Co0.3B in anaerobic conditions led to yet another metastable boride, Li0.01Ni0.7Co0.3B, with a CoB-type crystal structure that cannot be obtained by simple annealing of Ni, Co, and B. No significant alterations of magnetic properties were detected upon Co-doping in the temperature-independent paramagnet LiNi0.7Co0.3B or its Li-deintercalated counterparts. Finally, Li0.01Ni0.7Co0.3B stands out as an exceptional catalyst for the selective hydrogenation of the vinyl CâC bond in 3-nitrostyrene, even in the presence of other competing functional groups. This research showcases an innovative approach to heterogeneous catalyst design by meticulously synthesizing metastable compounds.
RESUMEN
Solid-state nuclear magnetic resonance can be enhanced using unpaired electron spins with a method known as dynamic nuclear polarization (DNP). Fundamentally, DNP involves ensembles of thousands of spins, a scale that is difficult to match computationally. This scale prevents us from gaining a complete understanding of the spin dynamics and applying simulations to design sample formulations. We recently developed an ab initio model capable of calculating DNP enhancements in systems of up to â¼1000 nuclei; however, this scale is insufficient to accurately simulate the dependence of DNP enhancements on radical concentration or magic angle spinning (MAS) frequency. We build on this work by using ab initio simulations to train a hybrid model that makes use of a rate matrix to treat nuclear spin diffusion. We show that this model can reproduce the MAS rate and concentration dependence of DNP enhancements and build-up time constants. We then apply it to predict the DNP enhancements in core-shell metal-organic-framework nanoparticles and reveal new insights into the composition of the particles' shells.
RESUMEN
Hydroformylation is an imperative chemical process traditionally catalyzed by homogeneous catalysts. Designing a heterogeneous catalyst with high activity and selectivity in hydroformylation is challenging but essential to allow the convenient separation and recycling of precious catalysts. Here, we report the development of an outstanding catalyst for efficient heterogeneous hydroformylation, RhZn intermetallic nanoparticles. In the hydroformylation of styrene, it shows three times higher turnover frequency (3090 h-1) compared to the benchmark homogeneous Wilkinson's catalyst (966 h-1), as well as a high chemoselectivity toward aldehyde products. RhZn is active for a variety of olefin substrates and can be recycled without a significant loss of activity. Density functional theory calculations show that the RhZn surfaces reduce the binding strength of reaction intermediates and have lower hydroformylation activation energy barriers compared to pure Rh(111), leading to more favorable reaction energetics on RhZn. The calculations also predict potential catalyst design strategies to achieve high regioselectivity.
RESUMEN
INTRODUCTION: Sleep disturbance, especially obstructive sleep apnea (OSA) and inadequate sleep, adversely affect various health-related quality of life (HR-QoL) domains in adults. Few studies have addressed problems with HR-QoL in children with OSA or sleep-related symptoms. METHODS: Patients between ages 5 to 17 years who were referred to the sleep laboratory from June 2017 to August 2017 for overnight polysomnography were approached to participate in the study. RESULTS: A total of 86 patients were included in the final analysis; 45 patients (52.3%) were male; and the median (interquartile range) of their mean BMI z-scores was 1.7 (0.5, 2.4). The patients were categorized by OSA severity as follows: 27 (31.4%) mild OSA, 11 (12.8%) moderate OSA, 24 (27.9%) severe OSA, and 24 (27.9%) without OSA. Severity of OSA was not correlated with any PROMIS domain. In univariable analyses, BMI z-score was negatively correlated with physical function mobility score (P = .002) and positively correlated with pain interference (P = .02) and pain intensity (P = .02). Total sleep time was positively correlated with physical function mobility (P = .03) and peer relationship (P = .002). Significant correlations between several PROMIS domains were also observed. CONCLUSIONS: Total sleep time was associated with physical function mobility and peer relationship. Regression analysis demonstrated a relationship between BMI z-score, physical function mobility, and pain intensity in our study population. COMMENTARY: A commentary on this article appears in this issue on page 541.
Asunto(s)
Índice de Masa Corporal , Dolor/complicaciones , Rendimiento Físico Funcional , Polisomnografía , Sueño/fisiología , Apoyo Social , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Dolor/fisiopatología , Polisomnografía/estadística & datos numéricos , Calidad de Vida , Apnea Obstructiva del Sueño/etiología , Apnea Obstructiva del Sueño/fisiopatologíaRESUMEN
Computer design and chemical synthesis generated viable variants of poliovirus type 1 (PV1), whose ORF (6,189 nucleotides) carried up to 1,297 "Max" mutations (excess of overrepresented synonymous codon pairs) or up to 2,104 "SD" mutations (randomly scrambled synonymous codons). "Min" variants (excess of underrepresented synonymous codon pairs) are nonviable except for P2Min, a variant temperature-sensitive at 33 and 39.5 °C. Compared with WT PV1, P2Min displayed a vastly reduced specific infectivity (si) (WT, 1 PFU/118 particles vs. P2Min, 1 PFU/35,000 particles), a phenotype that will be discussed broadly. Si of haploid PV presents cellular infectivity of a single genotype. We performed a comprehensive analysis of sequence and structures of the PV genome to determine if evolutionary conserved cis-acting packaging signal(s) were preserved after recoding. We showed that conserved synonymous sites and/or local secondary structures that might play a role in determining packaging specificity do not survive codon pair recoding. This makes it unlikely that numerous "cryptic, sequence-degenerate, dispersed RNA packaging signals mapping along the entire viral genome" [Patel N, et al. (2017) Nat Microbiol 2:17098] play the critical role in poliovirus packaging specificity. Considering all available evidence, we propose a two-step assembly strategy for +ssRNA viruses: step I, acquisition of packaging specificity, either (a) by specific recognition between capsid protein(s) and replication proteins (poliovirus), or (b) by the high affinity interaction of a single RNA packaging signal (PS) with capsid protein(s) (most +ssRNA viruses so far studied); step II, cocondensation of genome/capsid precursors in which an array of hairpin structures plays a role in virion formation.
Asunto(s)
Genoma Viral , Poliomielitis/virología , Poliovirus/genética , Poliovirus/patogenicidad , Virión/genética , Ensamble de Virus , Replicación Viral , Células A549 , Células HeLa , Humanos , Fenotipo , Poliomielitis/genética , ARN ViralRESUMEN
Herpesviruses establish life-long chronic infections that place infected hosts at risk for severe disease. Herpesvirus genomes readily undergo homologous recombination (HR) during productive replication, often leading to wild-type (WT) reversion during complementation of replication-defective and attenuated viruses via HR with the helper gene provided in trans. To overcome this barrier, we developed a synthetic-biology approach based on a technique known as codon shuffling. Computer-assisted algorithms redistribute codons in a helper gene, thereby eliminating regions of homology, while enabling manipulation of factors such as codon-pair bias and CpG content to effectively titrate helper-gene protein levels. We apply this technique to rescue the replication of a murine gammaherpesvirus engineered with a mutation in the major immediate-early transactivator protein RTA. Complementation with codon-shuffled RTA constructs did not yield any WT revertant virus, a sharp contrast to WT virus contamination frequently observed during complementation with an unmodified helper gene. We further demonstrate the importance of eliminating WT virus contamination in an animal model of gammaherpesvirus lethality. We propose complementation by codon shuffling as a means to produce replication-defective or attenuated viruses. This method has immediate utility for investigating roles of essential genes in viral replication and will better enable future development of herpesvirus vaccines.
Asunto(s)
Codón/química , Gammaherpesvirinae/genética , Regulación Viral de la Expresión Génica , Ingeniería Genética/métodos , Virus Helper/genética , Proteínas Inmediatas-Precoces/genética , Transactivadores/genética , Algoritmos , Animales , Emparejamiento Base , Línea Celular , Codón/metabolismo , Femenino , Fibroblastos/virología , Gammaherpesvirinae/metabolismo , Células HEK293 , Virus Helper/metabolismo , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/prevención & control , Infecciones por Herpesviridae/virología , Vacunas contra Herpesvirus/biosíntesis , Vacunas contra Herpesvirus/genética , Recombinación Homóloga , Humanos , Proteínas Inmediatas-Precoces/inmunología , Ratones , Ratones SCID , Transactivadores/inmunología , Replicación Viral/genéticaRESUMEN
Although the Hertz-Knudsen (HK) relation is often used to correlate evaporation data, the relation contains two empirical parameters (the evaporation and condensation coefficients) that have inexplicably been found to span 3 orders of magnitude. Explicit expressions for these coefficients have yet to be determined. This review will examine sources of error in the HK relation that have led to the coefficients' scatter. Through an examination of theoretical, experimental, and molecular dynamics simulation studies of evaporation, this review will show that the HK relation is incomplete, since it is missing an important physical concept: the coupling between the vapor and liquid phases during evaporation. The review also examines a modified HK relation, obtained from the quantum-mechanically based statistical rate theory (SRT) expression for the evaporation flux and applying a limit to it in which the thermal energy is dominant. Explicit expressions for the evaporation and condensation coefficients are defined in this limit, with the surprising result that the coefficients are not bounded by unity. An examination is made with 127 reported evaporation experiments of water and of ethanol, leading to a new physical interpretation of the coefficients. The review concludes by showing how seemingly small simplifications, such as assuming thermal equilibrium across the liquid-vapor interface during evaporation, can lead to the erroneous predictions from the HK relation that have been reported in the literature.
RESUMEN
Breast cancer is a leading source of malpractice claims for radiologists and gynecologists. Delay in or failure to diagnosis was the second most common cause for allegations of malpractice and failure to diagnosis breast cancer accounted for the majority of these claims. The amount paid in indemnity for such claims was only second to claims paid for neurologically impaired newborns. Issues involved in documentation and communication are reviewed with a focus on specific medical legal cases. Obstetrician gynecologists must remain cognizant of the potential for liability.
Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Ginecología/legislación & jurisprudencia , Responsabilidad Legal , Mala Praxis/legislación & jurisprudencia , Radiología/legislación & jurisprudencia , Gestión de Riesgos/métodos , Comunicación , Documentación , Detección Precoz del Cáncer , Femenino , Humanos , Gestión de Riesgos/legislación & jurisprudenciaRESUMEN
The protein synthesis machineries of two distinct phyla of the Animal kingdom, insects of Arthropoda and mammals of Chordata, have different preferences for how to best encode proteins. Nevertheless, arboviruses (arthropod-borne viruses) are capable of infecting both mammals and insects just like arboviruses that use insect vectors to infect plants. These organisms have evolved carefully balanced genomes that can efficiently use the translational machineries of different phyla, even if the phyla belong to different kingdoms. Using dengue virus as an example, we have undone the genome encoding balance and specifically shifted the encoding preference away from mammals. These mammalian-attenuated viruses grow to high titers in insect cells but low titers in mammalian cells, have dramatically increased LD50s in newborn mice, and induce high levels of protective antibodies. Recoded arboviruses with a bias toward phylum-specific expression could form the basis of a new generation of live attenuated vaccine candidates.
Asunto(s)
Arbovirus/fisiología , Genoma Viral , Insectos Vectores/virología , Mamíferos/virología , Animales , Animales Recién Nacidos , Anticuerpos Antivirales/inmunología , Arbovirus/genética , Línea Celular , Línea Celular Tumoral , Chlorocebus aethiops , Codón , Virus del Dengue/genética , Virus del Dengue/inmunología , Virus del Dengue/fisiología , Regulación Viral de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Humanos , Insectos Vectores/citología , Insectos Vectores/genética , Mamíferos/genética , Ratones Endogámicos ICR , Datos de Secuencia Molecular , ARN Helicasas/genética , ARN Helicasas/inmunología , ARN Helicasas/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serina Endopeptidasas/genética , Serina Endopeptidasas/inmunología , Serina Endopeptidasas/metabolismo , Vacunas Atenuadas/inmunología , Células Vero , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/inmunología , Proteínas no Estructurales Virales/metabolismo , Virosis/inmunología , Virosis/virologíaRESUMEN
A procedure for determining the structure of vapour and gas adsorbates that is based on the Zeta adsorption isotherm is reported. For vapours and for gases, this isotherm supposes that an adsorbate consists of particle clusters with the number of particles in a cluster denoted ζ, where ζ can be 1, 2, 3 up to a maximum of ζm, and predicts the isotherm constants are independent of pressure. For vapours, this allows the isotherm constants to be determined from isotherm measurements made at pressures less than the saturation-vapour pressure, Ps, but applied at pressures greater than Ps. Since ζ has an upper limit, we show that there are no singularities in the vapour or gas adsorption isotherms for any pressure. This allows the adsorption of vapours at pressures greater than Ps to be investigated: clusters with ζm molecules are predicted to increase in number as P(V) is increased, until they form an adsorbed film with each adsorption site occupied by a ζm-cluster. We apply the same procedure to determine the value of ζm for gas adsorption. For CO adsorbing on Ni(100), ζm is predicted to be unity for all the cases considered, indicating that the adsorbate consists of adsorbed molecules without any clustering. For H2 adsorption on the three different materials, ζm is found to be two: indicating the adsorbate consists of both adsorbed molecules and atoms. For each material considered, a pressure is predicted where the mole fractions of both are equal, and at higher pressure, the mole fraction of adsorbed molecules exceeds that of the adsorbed atoms.
RESUMEN
Autism remains an idiopathic disorder in 90% of cases. Recent prevalence, heritability, and genetic studies are suggestive that epigenetic and, therefore, environmental factors are important in autism pathogenesis. Among the environmental factors, only some uncommon viral infections and certain drugs have been conclusively linked to autism causation. Thalidomide, valproate, terbutaline and, most recently, antidepressants are the main drugs reported to elevate autism risk. This article discusses a phenomenal relationship between the drugs reported to elevate autism risk and the antiproliferative effects of the same drugs and/or analogs of the drugs in cancer cells. Cancer treatment has entered a new era-epigenetic therapy. In cancer cell lines, thalidomide is antiangiogenic and antiproliferative via suppression of tumor necrosis factor-alpha (TNF-α) and downstream effects on the nuclear factor (NFκB) cascade. Valproate shares similar mechanisms with thalidomide, but is best known in cancer therapy for its epigenetic effects as a histone deacetylase inhibitor. Terbutaline, a beta-adrenergic agonist, acts via adenylyl cyclase and cAMP-PKA signal transduction. Current cancer therapy aims to exploit this epigenetic pathway by developing site-selective cAMP analogs. Last, it has long been noted in preclinical studies that some antidepressants are antiproliferative in cancer cells but the mechanisms remain unclear. Based on a systematic review of these drugs, it is hypothesized that all central nervous system-acting drugs, which show antiproliferative effects in cancer cell lines, share the potential to elevate autism risk when administered prenatally. It is further posited that, in autism, the drugs act as "triggers" that disturb the pro-proliferative fetal milieu using the same, mainly epigenetic, mechanisms that they demonstrate in rapidly proliferating cancer cells. In addition to their direct antiproliferative effects, evidence is suggestive that the drugs may lock in the pro-inflammatory bias of the prenatal immune system by preventing normal perinatal dendritic cell maturation. This unifying hypothesis for how structurally different drugs elevate autism risk could help focus research on other drugs, or other xenobiotics, that may elevate autism risk. For example, there is evidence that an old class of drugs, the phenothiazines, is antiproliferative in cancer cell lines via inhibition of calmodulin and/or histaminic pathways. Promethazine, one of the first heterocyclic phenothiazines synthesized, is commonly prescribed during pregnancy; however, its role in elevating the risk of autism has not been investigated. Based on the anti-proliferation hypothesis, more studies of promethazine and other similar drugs are suggested to evaluate their potential to elevate autism risk following prenatal exposures.
Asunto(s)
Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Trastorno Autístico/inducido químicamente , Represión Epigenética/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Humanos , Modelos Biológicos , Terbutalina , Talidomida , Ácido ValproicoRESUMEN
During sessile droplet evaporation, studies with IR thermography and shadowgraphs have indicated temperature pulsations. We confirm those observations with microthermocouples, but microthermocouples also indicate temperature pulsations in the atmosphere of the droplet. The pressure in this atmosphere pulsated as well and was correlated with the temperature pulsations in the droplet. Also, we find that if a droplet evaporates into its own vapor, there are no temperature or pressure pulsations. The pulsations occur only if the droplet evaporates into an atmosphere with a component having a heat of solution with the droplet when it adsorbs-absorbs. None of the currently proposed mechanisms for the temperature pulsations provide an explanation for the coupling between the temperature pulsations in the droplet and the vapor-phase pressure pulsations, and for the absence of the pulsations when the system is single-component. As a mechanism for the pulsations, we propose that when a droplet is exposed to an atmosphere containing a component that has a heat of solution with the droplet, energy will be released from adsorption-absorption. This energy will cause pulsations in the evaporation flux, and these pulsations could cause the observed temperature and pressure pulsations. We examine this mechanism by showing that, if the measured temperature pulsations in a water droplet exposed to a methanol atmosphere are used as the input to a theory of evaporation kinetics (statistical rate theory), the pressure pulsations of the water vapor in the methanol atmosphere are predicted and agree with those measured with a quadrupole mass analyzer. When the inputs and outputs are reversed in the theory, we find that the temperature pulsations in the droplet are correctly predicted from the measured water vapor pulsations in the atmosphere.
RESUMEN
Genomes of RNA viruses contain multiple functional RNA elements required for translation or RNA replication. We use unique approaches to identify functional RNA elements in the coding sequence of poliovirus (PV), a plus strand RNA virus. The general method is to recode large segments of the genome using synonymous codons, such that protein sequences, codon use, and codon pair bias are conserved but the nucleic acid sequence is changed. Such recoding does not affect the growth of PV unless it destroys the sequence/structure of a functional RNA element. Using genetic analyses and a method called "signal location search," we detected two unique functionally redundant RNA elements (α and ß), each about 75 nt long and separated by 150 nt, in the 3'-terminal coding sequence of RNA polymerase, 3D(pol). The presence of wild type (WT) α or ß was sufficient for the optimal growth of PV, but the alteration of both segments in the same virus yielded very low titers and tiny plaques. The nucleotide sequences and predicted RNA structures of α and ß have no apparent resemblance to each other. In α, we narrowed down the functional domain to a 48-nt-long, highly conserved segment. The primary determinant of function in ß is a stable and highly conserved hairpin. Reporter constructs showed that the α- and ß-segments are required for RNA replication. Recoding offers a unique and effective method to search for unknown functional RNA elements in coding sequences of RNA viruses, particularly if the signals are redundant in function.
Asunto(s)
Diseño Asistido por Computadora , ARN Polimerasas Dirigidas por ADN/genética , Ingeniería Genética/métodos , Poliovirus/genética , ARN Viral/genética , Replicación Viral/genética , Poliovirus/crecimiento & desarrollo , Estructura Terciaria de Proteína/genéticaRESUMEN
Chronic pain is a common and costly experience. Cognitive behavioral therapies (CBT) are efficacious for an array of chronic pain conditions. However, the literature is based primarily on urban (white) samples. It is unknown whether CBT works in low-socioeconomic status (SES) minority and nonminority groups. To address this question, we conducted a randomized controlled trial within a low-SES, rural chronic pain population. Specifically, we examined the feasibility, tolerability, acceptability, and efficacy of group CBT compared with a group education intervention (EDU). We hypothesized that although both interventions would elicit short- and long-term improvement across pain-related outcomes, the cognitively-focused CBT protocol would uniquely influence pain catastrophizing. Mixed design analyses of variance were conducted on the sample of eligible participants who did not commence treatment (N=26), the intention-to-treat sample (ITT; N=83), and the completer sample (N=61). Factors associated with treatment completion were examined. Results indicated significantly more drop-outs occurred in CBT. ITT analyses showed that participants in both conditions reported significant improvement across pain-related outcomes, and a nonsignificant trend was found for depressed mood to improve more in CBT than EDU. Results of the completer analyses produced a similar pattern of findings; however, CBT produced greater gains on cognitive and affect variables than EDU. Treatment gains were maintained at 6-month follow-up (N=54). Clinical significance of the findings and the number of treatment responders is reported. Overall, these findings indicate that CBT and EDU are viable treatment options in low-SES minority and nonminority groups. Further research should target disseminating and sustaining psychosocial treatment options within underserved populations.
Asunto(s)
Analgesia/métodos , Dolor Crónico/psicología , Dolor Crónico/terapia , Terapia Cognitivo-Conductual/métodos , Educación del Paciente como Asunto/métodos , Psicoterapia de Grupo/métodos , Población Rural , Adulto , Dolor Crónico/prevención & control , Femenino , Humanos , Alfabetización Informacional , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto/normasRESUMEN
Adeno-associated virus (AAV) is a single-stranded parvovirus retaining the unique capacity for site-specific integration into a transcriptionally silent region of the human genome, a characteristic requiring the functional properties of the Rep 78/68 polypeptide in conjunction with AAV terminal repeat integrating elements. Previous strategies designed to assemble these genetic elements into adenoviral (Ad) backbones have been limited by the general intolerability of AAV Rep sequences, prompting us to computationally reengineer the Rep gene by using synonymous codon pair recoding. Rep mutants generated by using de novo genome synthesis maintained the polypeptide sequence and endonuclease properties of Rep 78, while dramatically enhancing Ad replication and viral titer yields, characteristics indistinguishable from adenovirus lacking coexpressed Rep. Parallel approaches using domain swaps encompassing WT and recoded genomic segments, coupled with iterative computational algorithms, collectively established that 3' cis-acting Rep genetic elements (and not the Rep 78 polypeptide) retain dominant-acting sequences inhibiting Ad replication. These data provide insights into the molecular relationships of AAV Rep and Ad replication, while expanding the applicability of synonymous codon pair reengineering as a strategy to effect phenotypic endpoints.
Asunto(s)
Biología Computacional/métodos , Dependovirus/genética , Vectores Genéticos/genética , Proteínas Virales/genética , Secuencia de Bases , Codón/genética , Dependovirus/fisiología , Endonucleasas/metabolismo , Genes Virales/genética , Células HEK293 , Células HeLa , Humanos , Mutación/genética , Proteínas Virales/metabolismo , Replicación Viral/fisiologíaRESUMEN
Despite existing vaccines and enormous efforts in biomedical research, influenza annually claims 250,000-500,000 lives worldwide, motivating the search for new, more effective vaccines that can be rapidly designed and easily produced. We applied the previously described synthetic attenuated virus engineering (SAVE) approach to influenza virus strain A/PR/8/34 to rationally design live attenuated influenza virus vaccine candidates through genome-scale changes in codon-pair bias. As attenuation is based on many hundreds of nucleotide changes across the viral genome, reversion of the attenuated variant to a virulent form is unlikely. Immunization of mice by a single intranasal exposure to codon pair-deoptimized virus conferred protection against subsequent challenge with wild-type (WT) influenza virus. The method can be applied rapidly to any emerging influenza virus in its entirety, an advantage that is especially relevant when dealing with seasonal epidemics and pandemic threats, such as H5N1- or 2009-H1N1 influenza.
Asunto(s)
Diseño Asistido por Computadora , Orthomyxoviridae/inmunología , Vacunas Virales , Animales , Células Cultivadas , Codón , Perros , Genoma Viral , Dosificación Letal Mediana , Ratones , Datos de Secuencia Molecular , Orthomyxoviridae/genéticaRESUMEN
OBJECTIVE: Preclinical and clinical studies demonstrate a hyperactivity of the norepinephrine system in patients with posttraumatic stress disorder (PTSD). a(2) adrenergic agonists have been shown to ameliorate symptoms of PTSD, likely because of their ability to dampen noradrenergic tone. This study tests the ability of the a(2) adrenergic agonist, guanfacine, to reduce the symptoms of PTSD. EXPERIMENTAL DESIGN: Patients with chronic PTSD were randomized (1:1) to an 8-week double-blind, placebo-controlled treatment of guanfacine followed by a 2 month open label extension phase. Patients were maintained on their stable doses of allowed antidepressants during the trial. Efficacy was measured by the following assessment scales: Clinician Administered PTSD Scale (CAPS), Montgomery Asberg Depression Rating Scale (MADRS), Clinical Global Impression-Severity (CGI-S), Clinical Global Impression-Improvement (CGI-I), and Davidson Trauma Scale (DTS, self-report). PRINCIPAL OBSERVATIONS: There were no significant differences in the drug versus placebo responses for the clinician-administered or patient self-report outcome measures in this small sample of predominantly male combat veterans with PTSD. However, the medication was well tolerated. CONCLUSION: Similar to previous findings, this small pilot study failed to show differences in the response to guanfacine versus placebo in a small sample of predominantly male combat veterans with PTSD.
Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Guanfacina/uso terapéutico , Trastornos por Estrés Postraumático/tratamiento farmacológico , Adulto , Anciano , Método Doble Ciego , Femenino , Guanfacina/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , VeteranosRESUMEN
Thermocapillary convection has a very different history for water than for other liquids. For water, several studies have pointed to the lack of evidence supporting the existence of thermocapillary (or Marangoni) convection. Other studies have given clear evidence of its existence and of the role it plays during steady-state water evaporation. We examine both sets of data and suggest a reason for the difference in the interpretation of the experimental data. For organic liquids, the evidence of thermocapillary convection has been clearly documented, but the issues are the type of flow that it generates during steady-state evaporation. We review the measurements and show that the flow field of the evaporating liquid is strongly affected by the presence of the thermocapillary convection. When the results obtained from both water and organic liquids are compared, they give further insight into the nature of thermocapillary convection.
RESUMEN
OBJECTIVE: Establish a 3-year hospital internship within a drug use and disease state management program that would provide doctor of pharmacy students with experiential learning while still completing their classroom studies. DESIGN: As paid interns, students engaged in group and individual activities that assessed clinical practice guidelines. Patient monitoring and clinical intervention techniques were learned through prospective evaluation of drug therapy. Students designed evidence-based treatment guidelines and participated in all phases of development, including multidisciplinary approval, implementation, and evaluation stages. ASSESSMENT: Student competency was continually monitored through direct observation by a preceptor and written examinations. Patient case studies, group discussions, and poster presentations allowed assessment of student growth in knowledge and communication skills. CONCLUSION: The comprehensive structure of this internship provides a broad perspective for understanding the role of the hospital pharmacist in providing pharmaceutical care. Close supervision maximizes student learning potential and fosters a mentoring relationship for both personal and professional growth.