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1.
Proc Natl Acad Sci U S A ; 120(2): e2215509119, 2023 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-36608295

RESUMEN

Recently, Co-based honeycomb magnets have been proposed as promising candidate materials to host the Kitaev spin liquid (KSL) state. One of the front-runners is BaCo2(AsO4)2 (BCAO), where it was suggested that the exchange processes between Co2+ ions via the surrounding edge-sharing oxygen octahedra could give rise to bond-dependent Kitaev interactions. In this work, we present and analyze a comprehensive inelastic neutron scattering (INS) study of BCAO with fields in the honeycomb plane. Combining the constraints from the magnon excitations in the high-field polarized state and the inelastic spin structure factor measured in zero magnetic field, we examine two leading theoretical models: the Kitaev-type [Formula: see text] model and the XXZ[Formula: see text]model. We show that the existing experimental data can be consistently accounted for by the XXZ[Formula: see text]model but not by the [Formula: see text] model, and we discuss the implications of these results for the realization of a spin liquid phase in BCAO and more generally for the realization of the Kitaev model in cobaltates.

2.
Scand J Med Sci Sports ; 33(12): 2470-2481, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37787091

RESUMEN

Studies examining the effect of protein (PRO) feeding on post resistance exercise (RE) muscle protein synthesis (MPS) have primarily been performed in men, and little evidence is available regarding the quantity of PRO required to maximally stimulate MPS in trained women following repeated bouts of RE. We therefore quantified acute (4 h and 8 h) and extended (24 h) effects of two bouts of resistance exercise, alongside protein-feeding, in women, and the PRO requirement to maximize MPS. Twenty-four RE trained women (26.6 ± 0.7 years, mean ± SEM) performed two bouts of whole-body RE (3 × 8 repetitions/maneuver at 75% 1-repetition maximum) 4 h apart, with post-exercise ingestion of 15 g, 30 g, or 60 g whey PRO (n = 8/group). Saliva, venous blood, and a vastus lateralis muscle biopsy were taken at 0 h, 4 h, 8 h, and 24 h post-exercise. Plasma leucine and branched chain amino acids were quantified using gas chromatography mass spectrometry (GC-MS) after ingestion of D2 O. Fifteen grams PRO did not alter plasma leucine concentration or myofibrillar synthetic rate (MyoFSR). Thirty and sixty grams PRO increased plasma leucine concentration above baseline (105.5 ± 5.3 µM; 120.2 ± 7.4 µM, respectively) at 4 h (151.5 ± 8.2 µM, p < 0.01; 224.8 ± 16.0 µM, p < 0.001, respectively) and 8 h (176.0 ± 7.3 µM, p < 0.001; 281.7 ± 21.6 µM, p < 0.001, respectively). Ingestion of 30 g PRO increased MyoFSR above baseline (0.068 ± 0.005%/h) from 0 to 4 h (0.140 ± 0.021%/h, p < 0.05), 0 to 8 h (0.121 ± 0.012%/h, p < 0.001), and 0 to 24 h (0.099 ± 0.011%/h, p < 0.01). Ingestion of 60 g PRO increased MyoFSR above baseline (0.063 ± 0.003%/h) from 0 to 4 h (0.109 ± 0.011%/h, p < 0.01), 0 to 8 h (0.093 ± 0.008%/h, p < 0.01), and 0 to 24 h (0.086 ± 0.006%/h, p < 0.01). Post-exercise ingestion of 30 g or 60 g PRO, but not 15 g, acutely increased MyoFSR following two consecutive bouts of RE and extended the anabolic window over 24 h. There was no difference between the 30 g and 60 g responses.


Asunto(s)
Entrenamiento de Fuerza , Masculino , Humanos , Femenino , Leucina/metabolismo , Leucina/farmacología , Proteína de Suero de Leche , Músculo Esquelético/metabolismo , Proteínas Musculares/metabolismo
3.
Ultrasound Obstet Gynecol ; 57(5): 769-775, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-32202689

RESUMEN

OBJECTIVE: Fetal cerebrovascular resistance is influenced by several factors in the setting of intact autoregulation to allow for normal cerebral blood flow and oxygenation. Maternal hyperoxygenation (MH) allows for acute alterations in fetal physiology and can be a tool to test cerebrovascular reactivity in late-gestation fetuses. In this study, we utilized MH to evaluate cerebrovascular reactivity in fetuses with specific congenital heart disease (CHD). METHODS: This was a cross-sectional study of fetuses with complex CHD compared to controls without CHD. CHD cases were grouped according to physiology into: left-sided obstructive lesion (LSOL), right-sided obstructive lesion (RSOL) or dextro-transposition of the great arteries (d-TGA). Subjects underwent MH testing during the third-trimester fetal echocardiogram. The pulsatility index (PI) was calculated for the fetal middle cerebral artery (MCA), umbilical artery (UA) and branch pulmonary artery (PA). The change in PI from baseline to during MH was compared between each CHD group and controls. RESULTS: Sixty pregnant women were enrolled (CHD, n = 43; control, n = 17). In the CHD group, there were 27 fetuses with LSOL, seven with RSOL and nine with d-TGA. Mean gestational age was 33.9 (95% CI, 33.6-34.2) weeks. At baseline, MCA-PI Z-score was lowest in the LSOL group (-1.8 (95% CI, -2.4 to -1.2)) compared with the control group (-0.8 (95% CI, -1.3 to -0.3)) (P = 0.01). In response to MH, MCA-PI Z-score increased significantly in the control and d-TGA groups but did not change significantly in the LSOL and RSOL groups. The change in MCA-PI Z-score was significantly higher in the control group than in the LSOL group (0.9 (95% CI, 0.42-1.4) vs 0.12 (95% CI, -0.21 to 0.45); P = 0.03). This difference was more pronounced in the LSOL subgroup with retrograde aortic arch flow. Branch PA-PI decreased significantly in response to MH in all groups, with no difference in the change from baseline to MH between the groups, while UA-PI was unchanged during MH compared with at baseline. CONCLUSIONS: The fetal cerebrovascular response to MH varies based on the underlying CHD diagnosis, suggesting that cardiovascular physiology may influence the autoregulatory capacity of the fetal brain. Further studies are needed to determine the clinical implications of these findings on long-term neurodevelopment in these at-risk children. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.


Asunto(s)
Circulación Cerebrovascular , Terapias Fetales/métodos , Cardiopatías Congénitas/embriología , Terapia por Inhalación de Oxígeno/métodos , Circulación Placentaria , Adaptación Fisiológica , Adulto , Estudios de Casos y Controles , Estudios Transversales , Ecocardiografía , Femenino , Feto/embriología , Feto/fisiopatología , Edad Gestacional , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/fisiopatología , Humanos , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/embriología , Arteria Cerebral Media/fisiopatología , Embarazo , Tercer Trimestre del Embarazo , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/embriología , Arteria Pulmonar/fisiopatología , Flujo Pulsátil , Ultrasonografía Prenatal , Arterias Umbilicales/diagnóstico por imagen , Arterias Umbilicales/embriología , Arterias Umbilicales/fisiopatología
4.
Am J Physiol Endocrinol Metab ; 318(6): E943-E955, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32369414

RESUMEN

Myokines, such as irisin, have been purported to exert physiological effects on skeletal muscle in an autocrine/paracrine fashion. In this study, we aimed to investigate the mechanistic role of in vivo fibronectin type III domain-containing 5 (Fndc5)/irisin upregulation in muscle. Overexpression (OE) of Fndc5 in rat hindlimb muscle was achieved by in vivo electrotransfer, i.e., bilateral injections of Fndc5 harboring vectors for OE rats (n = 8) and empty vector for control rats (n = 8). Seven days later, a bolus of D2O (7.2 mL/kg) was administered via oral gavage to quantify muscle protein synthesis. After an overnight fast, on day 9, 2-deoxy-d-glucose-6-phosphate (2-DG6P; 6 mg/kg) was provided during an intraperitoneal glucose tolerance test (2 g/kg) to assess glucose handling. Animals were euthanized, musculus tibialis cranialis muscles and subcutaneous fat (inguinal) were harvested, and metabolic and molecular effects were evaluated. Muscle Fndc5 mRNA increased with OE (~2-fold; P = 0.014), leading to increased circulating irisin (1.5 ± 0.9 to 3.5 ± 1.2 ng/mL; P = 0.049). OE had no effect on protein anabolism or mitochondrial biogenesis; however, muscle glycogen was increased, along with glycogen synthase 1 gene expression (P = 0.04 and 0.02, respectively). In addition to an increase in glycogen synthase activation in OE (P = 0.03), there was a tendency toward increased glucose transporter 4 protein (P = 0.09). However, glucose uptake (accumulation of 2-DG6P) was identical. Irisin elicited no endocrine effect on mitochondrial biogenesis or uncoupling proteins in white adipose tissue. Hindlimb overexpression led to physiological increases in Fndc5/irisin. However, our data indicate limited short-term impacts of irisin in relation to muscle anabolism, mitochondrial biogenesis, glucose uptake, or adipose remodeling.


Asunto(s)
Fibronectinas/genética , Músculo Esquelético/metabolismo , Grasa Subcutánea/metabolismo , Animales , Desoxiglucosa/metabolismo , Óxido de Deuterio , Electroporación , Fibronectinas/metabolismo , Expresión Génica , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Transportador de Glucosa de Tipo 4/genética , Glucosa-6-Fosfato/análogos & derivados , Glucosa-6-Fosfato/metabolismo , Glucógeno/metabolismo , Glucógeno Sintasa/genética , Glucógeno Sintasa/metabolismo , Miembro Posterior , Masculino , Proteínas Desacopladoras Mitocondriales/genética , Biogénesis de Organelos , Biosíntesis de Proteínas , ARN Mensajero/metabolismo , Ratas
5.
Phys Rev Lett ; 125(2): 027201, 2020 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-32701305

RESUMEN

We measure the mode-resolved direction of the precessional motion of the magnetic order, i.e., magnon polarization, via the chiral term of inelastic polarized neutron scattering spectra. The magnon polarization is a unique and unambiguous signature of magnets and is important in spintronics, affecting thermodynamic properties such as the magnitude and sign of the spin Seebeck effect. However, it has never been directly measured in any material until this work. The observation of both signs of magnon polarization in Y_{3}Fe_{5}O_{12} also gives direct proof of its ferrimagnetic nature. The experiments agree very well with atomistic simulations of the scattering cross section.

6.
Nurs Adm Q ; 44(1): 78-86, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31789752

RESUMEN

Patient perception of caregiver empathy has been studied internationally for decades. Although leadership empathy has been described as having a critical influence on staff retention, this subject is less evident in the literature. This article described a study undertaken to gain a baseline understanding of nurses' perceptions of leader empathy from those they identify as their managers. A baseline for nurses' perception of leader empathy has been established that may be used to benchmark future interventions to assess and improve nurses' perception of their leaders' empathy in the work setting.


Asunto(s)
Actitud del Personal de Salud , Empatía , Enfermeras Administradoras , Personal de Enfermería en Hospital/psicología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Estados Unidos , Adulto Joven
7.
J Nerv Ment Dis ; 206(12): 950-954, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30439782

RESUMEN

This study examined help-seeking behavior from professional, informal, and religious sources in veterans with a probable need for treatment. In total, 93 veterans who screened positive for posttraumatic stress disorder/major depressive disorder completed assessments of help-seeking at two time points spaced apart by 6 months. Less than half (40%) reached out to a mental health professional or physician; only 1 in 10 engaged with providers who specialize in evidence-based therapies to a minimally adequate degree. Although roughly two thirds pursued help from informal sources, less than 10% similarly sought help nine or more times. Veterans with high willingness to seek help from specific sources at baseline were more likely to report sustained engagement in help-seeking behavior along these same lines at follow-up. Assessing veterans' help-seeking intentions may add prognostic value in predicting engagement in services. Veterans may also benefit from tailoring service delivery models according to preferred sources of help in their families and communities.


Asunto(s)
Trastorno Depresivo Mayor/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Trastornos por Estrés Postraumático/psicología , Veteranos/psicología , Adulto , Trastorno Depresivo Mayor/terapia , Femenino , Conducta de Búsqueda de Ayuda , Humanos , Masculino , Aceptación de la Atención de Salud/psicología , Escalas de Valoración Psiquiátrica , Trastornos por Estrés Postraumático/terapia , Encuestas y Cuestionarios , Estados Unidos , Veteranos/estadística & datos numéricos
8.
Clin Psychol Psychother ; 25(3): 474-488, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29282787

RESUMEN

There is consensus that military personnel can encounter a far more diverse set of challenges than researchers and clinicians have historically appreciated. Moral injury (MI) represents an emerging construct to capture behavioural, social, and spiritual suffering that may transcend and overlap with mental health diagnoses (e.g., post-traumatic stress disorder and major depressive disorder). The Expressions of Moral Injury Scale-Military Version (EMIS-M) was developed to provide a reliable and valid means for assessing the warning signs of a MI in military populations. Drawing on independent samples of veterans who had served in a war-zone environment, factor analytic results revealed 2 distinct factors related to MI expressions directed at both self (9 items) and others (8 items). These subscales generated excellent internal consistency and temporal stability over a 6-month period. When compared to measures of post-traumatic stress disorder, major depressive disorder, and other theoretically relevant constructs (e.g., forgiveness, social support, moral emotions, and combat exposure), EMIS-M scores demonstrated strong convergent, divergent, and incremental validity. In addition, although structural equation modelling findings supported a possible general MI factor in Study 2, the patterns of associations for self- and other-directed expressions yielded evidence for differential validity with varying forms of forgiveness and combat exposure. As such, the EMIS-M provides a face valid, psychometrically validated tool for assessing expressions of apparent MI subtypes in research and clinical settings. Looking ahead, the EMIS-M will hopefully advance the scientific understanding of MI while supporting innovation for clinicians to tailor evidence-based treatments and/or develop novel approaches for addressing MI in their work.


Asunto(s)
Principios Morales , Estrés Psicológico/diagnóstico , Estrés Psicológico/psicología , Veteranos/psicología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Estrés Psicológico/complicaciones , Veteranos/estadística & datos numéricos , Adulto Joven
9.
J Relig Health ; 57(6): 2444-2460, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30094678

RESUMEN

This study examines VA chaplains' understandings of moral injury (MI) and preferred intervention strategies. Drawing qualitative responses with a nationally-representative sample, content analyses indicated that chaplains' definitions of MI comprised three higher order clusters: (1) MI events, (2) mechanisms in development of MI, and (3) warning signs of MI. Similarly, chaplains' intervention foci could be grouped into three categories: (1) pastoral/therapeutic presence, (2) implementing specific interventions, and (3) therapeutic processes to promote moral repair. Findings are discussed related to emerging conceptualizations of MI, efforts to adapt existing evidence-based interventions to better address MI, and the potential benefits of better integrating chaplains into VA mental health service delivery.


Asunto(s)
Clero/psicología , Servicios de Salud Mental/organización & administración , Personal Militar/psicología , Cuidado Pastoral/organización & administración , Trastornos por Estrés Postraumático/psicología , Veteranos/psicología , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Investigación Cualitativa
10.
Am J Physiol Endocrinol Metab ; 313(6): E681-E689, 2017 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-28811296

RESUMEN

Current methods to quantify in vivo RNA dynamics are limited. Here, we developed a novel stable isotope (D2O) methodology to quantify RNA synthesis (i.e., ribosomal biogenesis) in cells, animal models, and humans. First, proliferating C2C12 cells were incubated in D2O-enriched media and myotubes ±50 ng/ml IGF-I. Second, rat quadriceps (untrained, n = 9; 7-wk interval-"like" training, n = 13) were collected after ~3-wk D2O (70 atom %) administration, with body-water enrichment monitored via blood sampling. Finally, 10 (23 ± 1 yr) men consumed 150-ml D2O followed by 50 ml/wk and undertook 6-wk resistance exercise (6 × 8 repetitions, 75% 1-repetition maximum 3/wk) with body-water enrichment monitored by saliva sampling and muscle biopsies (for determination of RNA synthesis) at 0, 3, and 6 wk. Ribose mole percent excess (r-MPE) from purine nucleotides was analyzed via GC-MS/MS. Proliferating C2C12 cell r-MPE exhibited a rise to plateau, whereas IGF-I increased myotube RNA from 76 ± 3 to 123 ± 3 ng/µl and r-MPE by 0.39 ± 0.1% (both P < 0.01). After 3 wk, rat quadriceps r-MPE had increased to 0.25 ± 0.01% (P < 0.01) and was greater with running exercise (0.36 ± 0.02%; P < 0.01). Human muscle r-MPE increased to 0.06 ± 0.01 and 0.13 ± 0.02% at 3/6 wk, respectively, equating to synthesis rates of ~0.8%/day, increasing with resistance exercise to 1.7 ± 0.3%/day (P < 0.01) and 1.2 ± 0.1%/day (P < 0.05) at 3/6 wk, respectively. Therefore, we have developed and physiologically validated a novel technique to explore ribosomal biogenesis in a multimodal fashion.


Asunto(s)
Biomarcadores/metabolismo , Óxido de Deuterio , Músculo Cuádriceps/metabolismo , ARN/biosíntesis , Ribosomas/metabolismo , Animales , Línea Celular , Femenino , Humanos , Masculino , Ratones , Condicionamiento Físico Animal , Ratas , Entrenamiento de Fuerza , Ribosa/metabolismo , Espectrometría de Masas en Tándem , Adulto Joven
11.
Ultrasound Obstet Gynecol ; 45(4): 447-51, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25157457

RESUMEN

OBJECTIVES: Twin-reversed arterial perfusion (TRAP) sequence affects 1% of monochorionic twin pregnancies and is caused by abnormal vascular connections between a pump twin and an acardiac mass. The effects of abnormal vascular connections on cerebral vasculature in the pump twin are unknown. We hypothesize that abnormal cerebral vascular impedance, as assessed by the pulsatility index (PI), is present in pump twins and that fetal intervention alters cerebral impedance. METHODS: Fetal echocardiograms performed between 2010 and 2013 in pregnancies diagnosed with TRAP (n = 19), recorded at presentation, and uncomplicated monochorionic twin pregnancies (controls, n = 18; 36 fetuses) were analyzed. In all subjects, the middle cerebral artery (MCA)-PI, combined cardiac output (CCO) and cardiothoracic ratio were calculated, and the values for cases and controls were compared. RESULTS: The mean gestational age at the time of echocardiography was 20 weeks in both groups. MCA-PI was lower in TRAP cases than in controls (1.55 (95% CI, 1.47-1.64) vs 1.74 (95% CI, 1.65-1.82), respectively; P = 0.004). CCO in TRAP cases was mildly elevated for gestational age (199.7 (95% CI, 138.4-261.1) mL/min) compared with that of controls (131.4 (95% CI, 102.2-160.7) mL/min). In six TRAP cases with a second echocardiogram available, the mean MCA-PI increased after intervention, from 1.5 (95% CI, 1.3-1.7) to 1.8 (95% CI, 1.4-2.2). CONCLUSIONS: TRAP pump twins have lower cerebral vascular impedance than do controls, suggestive of a brain-sparing effect. MCA-PI appeared to increase in a small group of pump twins after intervention. These findings suggest a fetal cerebral autoregulatory response to a high cardiac output state that begins to change after fetal intervention. The long-term implications for neurodevelopmental outcome warrant further study.


Asunto(s)
Transfusión Feto-Fetal/fisiopatología , Feto/irrigación sanguínea , Arteria Cerebral Media/diagnóstico por imagen , Gemelos , Ecocardiografía , Femenino , Transfusión Feto-Fetal/diagnóstico por imagen , Feto/anomalías , Humanos , Trastornos del Neurodesarrollo/diagnóstico por imagen , Trastornos del Neurodesarrollo/fisiopatología , Placenta/irrigación sanguínea , Placenta/diagnóstico por imagen , Embarazo , Embarazo Gemelar , Flujo Pulsátil/fisiología , Tratamiento de Radiofrecuencia Pulsada/métodos , Tasa de Supervivencia , Ultrasonografía Prenatal
12.
Ultrasound Obstet Gynecol ; 46(6): 688-94, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25597867

RESUMEN

OBJECTIVES: To assess whether severity of congenital diaphragmatic hernia (CDH) correlates with the degree of left heart hypoplasia and left ventricle (LV) output, and to determine if factors leading to abnormal fetal hemodynamics, such as compression and reduced LV preload, contribute to left heart hypoplasia. METHODS: This was a retrospective cross-sectional study of fetuses at 16-37 weeks' gestation that were diagnosed with CDH between 2000 and 2010. Lung-to-head ratio (LHR), liver position and side of the hernia were determined from stored ultrasound images. CDH severity was dichotomized based on LHR and liver position. The dimensions of mitral (MV) and aortic (AV) valves and LV were measured, and right and left ventricular outputs were recorded. RESULTS: In total, 188 fetuses with CDH were included in the study, 171 with left CDH and 17 with right CDH. Fetuses with severe left CDH had a smaller MV (Z = -2.24 ± 1.3 vs -1.33 ± 1.08), AV (Z = -1.39 ± 1.21 vs -0.51 ± 1.05) and LV volume (Z = -4.23 ± -2.71 vs -2.08 ± 3.15) and had lower LV output (26 ± 10% vs 32 ± 10%) than those with mild CDH. MV and AV in fetuses with right CDH (MV, Z = -0.83 ± 1.19 and AV, Z = -0.71 ± 1.07) were larger than those in fetuses with left CDH, but LV outputs were similarly diminished, regardless of hernia side. Severe dextroposition and abnormal liver position were associated independently with smaller left heart, while LHR was not. CONCLUSION: The severity of left heart hypoplasia correlates with the severity of CDH. Altered fetal hemodynamics, leading to decreased LV output, occurs in both right- and left-sided CDH, but the additional compressive effect on the left heart is seen only when the hernia is left-sided. Improved knowledge of the physiology of this disease may lead to advances in therapy and better risk assessment for use in counseling affected families.


Asunto(s)
Desarrollo Fetal , Enfermedades Fetales/diagnóstico por imagen , Corazón Fetal/diagnóstico por imagen , Hernias Diafragmáticas Congénitas/embriología , Síndrome del Corazón Izquierdo Hipoplásico/embriología , Estudios Transversales , Ecocardiografía/métodos , Femenino , Corazón Fetal/anatomía & histología , Edad Gestacional , Cabeza/diagnóstico por imagen , Cabeza/embriología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/embriología , Hernias Diafragmáticas Congénitas/complicaciones , Hernias Diafragmáticas Congénitas/diagnóstico por imagen , Humanos , Síndrome del Corazón Izquierdo Hipoplásico/diagnóstico por imagen , Hígado/diagnóstico por imagen , Hígado/embriología , Pulmón/diagnóstico por imagen , Pulmón/embriología , Tamaño de los Órganos , Embarazo , Estudios Retrospectivos , Ultrasonografía Prenatal/métodos
13.
BMC Infect Dis ; 14: 67, 2014 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-24502661

RESUMEN

BACKGROUND: The use of prototypic strains is common among laboratories studying infectious agents as it promotes consistency for data comparability among and between laboratories. Schu S4 is the prototypic virulent strain of Francisella tularensis and has been used extensively as such over the past six decades. Studies have demonstrated virulence differences among the two clinically relevant subspecies of F. tularensis, tularensis (type A) and holarctica (type B) and more recently between type A subpopulations (A1a, A1b and A2). Schu S4 belongs to the most virulent subspecies of F. tularensis, subspecies tularensis. METHODS: In this study, we investigated the relative virulence of Schu S4 in comparison to A1a, A1b, A2 and type B strains using a temperature-based murine model of infection. Mice were inoculated intradermally and a hypothermic drop point was used as a surrogate for death. Survival curves and the length of temperature phases were compared for all infections. Bacterial burdens were also compared between the most virulent type A subpopulation, A1b, and Schu S4 at drop point. RESULTS: Survival curve comparisons demonstrate that the Schu S4 strain used in this study resembles the virulence of type B strains, and is significantly less virulent than all other type A (A1a, A1b and A2) strains tested. Additionally, when bacterial burdens were compared between mice infected with Schu S4 or MA00-2987 (A1b) significantly higher burdens were present in the blood and spleen of mice infected with MA00-2987. CONCLUSIONS: The knowledge gained from using Schu S4 as a prototypic virulent strain has unquestionably advanced the field of tularemia research. The findings of this study, however, indicate that careful consideration of F. tularensis strain selection must occur when the overall virulence of the strain used could impact the outcome and interpretation of results.


Asunto(s)
Modelos Animales de Enfermedad , Francisella tularensis/clasificación , Francisella tularensis/patogenicidad , Tularemia/microbiología , Animales , Femenino , Francisella tularensis/aislamiento & purificación , Humanos , Pulmón/microbiología , Ratones , Ratones Endogámicos C57BL , Virulencia
14.
Am J Epidemiol ; 178(2): 249-59, 2013 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-23801013

RESUMEN

Having multiple sexual partners concurrently increases the risk of transmission of a sexually transmitted infection. Even if partnerships do not overlap, transmission potential exists when the gap between partnerships is shorter than the remaining infectious period. In the present article, we quantify the gap between partners to assess transmission potential using data collected by a cross-sectional survey of 2,203 genitourinary medicine clinic patients in England in 2009. Questionnaires asked about patients' 3 most recent partnerships. Gaps were calculated as time (days) between the last sexual encounter with a former partner and the first sexual encounter with the next partner. Among 1,875 patients who reported 1 or more partners in the previous 3 months, 47.6% of men and 27.7% of women reported 2 or more partners. Forty-two percent of the gaps were negative (i.e., partnerships that were concurrent); the median gaps were -7 and -17 days for men and women, respectively (i.e., overlaps were 7 and 17 days for men and women, respectively). Although half of the gaps were positive (serially monogamous partnerships), many were of short duration; the median gaps were 14 and 24 days for men and women, respectively. In over half of the gaps, condoms were used inconsistently with one or both partners, and in one-quarter, condoms were never used with either partner. There is thus a high potential for sexually transmitted infections, as even if partnerships are not behaviorally concurrent, they may be biologically concurrent. These data have important implications for designing and targeting effective health promotion messages.


Asunto(s)
Parejas Sexuales , Enfermedades de Transmisión Sexual/transmisión , Sexo Inseguro/estadística & datos numéricos , Adolescente , Adulto , Condones/estadística & datos numéricos , Estudios Transversales , Inglaterra , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de Transmisión Sexual/prevención & control , Encuestas y Cuestionarios , Factores de Tiempo , Adulto Joven
16.
Antimicrob Agents Chemother ; 56(1): 555-8, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22024826

RESUMEN

Yersinia pestis is the causative agent of plague, a fulminant disease that is often fatal without antimicrobial treatment. Plasmid (IncA/C)-mediated multidrug resistance in Y. pestis was reported in 1995 in Madagascar and has generated considerable public health concern, most recently because of the identification of IncA/C multidrug-resistant plasmids in other zoonotic pathogens. Here, we demonstrate no resistance in 392 Y. pestis isolates from 17 countries to eight antimicrobials used for treatment or prophylaxis of plague.


Asunto(s)
Antibacterianos/uso terapéutico , Peste/tratamiento farmacológico , Yersinia pestis/genética , África , Américas , Animales , Asia , Farmacorresistencia Bacteriana , Humanos , Madagascar , Pruebas de Sensibilidad Microbiana , Filogeografía , Peste/microbiología , Peste/transmisión , Plásmidos/genética , Salud Pública , Siphonaptera , Yersinia pestis/aislamiento & purificación
17.
J Vis Exp ; (179)2022 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-35129177

RESUMEN

The continued use of insecticides for public health and agriculture has led to widespread insecticide resistance and hampering of control methods. Insecticide resistance surveillance of mosquito populations is typically done through Centers for Disease Control and Prevention (CDC) bottle bioassays or World Health Organization (WHO) tube tests. However, these methods can result in a high degree of variability in mortality data due to variable insecticide contact with the insect, the relatively small numbers of organisms tested, extensive variation in mass between populations, and constantly changing environmental conditions, leading to variable outcomes. This paper presents the topical application bioassay, adapted as a high-throughput phenotypic bioassay for both mosquitoes and fruit flies, to test large numbers of insects along a range of insecticide concentrations. This assay 1) ensures consistent treatment and insecticide contact with every organism, 2) produces highly specific dose-response curves that account for differences in average mass between strains and sexes (which is particularly important for field-collected organisms), and 3) allows for the calculation of statistically rigorous median lethal doses (LD50), which are necessary for resistance ratio comparisons-an alternative surveillance approach from diagnostic dose mortality, which is also used for larvicide resistance surveillance. This assay will be a complementary tool for accurately phenotyping mosquito populations and, as illustrated using fruit flies, is easily adaptable for use with other insects. We argue that this assay will help fill the gap between genotypic and phenotypic insecticide resistance in multiple insect species.


Asunto(s)
Anopheles , Insecticidas , Animales , Bioensayo , Resistencia a los Insecticidas , Insecticidas/farmacología , Control de Mosquitos
18.
Pathogens ; 11(3)2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-35335607

RESUMEN

Many pathogens can cause cancer, but cancer itself does not normally act as an infectious agent. However, transmissible cancers have been found in a few cases in nature: in Tasmanian devils, dogs, and several bivalve species. The transmissible cancers in dogs and devils are known to spread through direct physical contact, but the exact route of transmission of bivalve transmissible neoplasia (BTN) has not yet been confirmed. It has been hypothesized that cancer cells from bivalves could be released by diseased animals and spread through the water column to infect/engraft into other animals. To test the feasibility of this proposed mechanism of transmission, we tested the ability of BTN cells from the soft-shell clam (Mya arenaria BTN, or MarBTN) to survive in artificial seawater. We found that MarBTN cells are highly sensitive to salinity, with acute toxicity at salinity levels lower than those found in the native marine environment. BTN cells also survive longer at lower temperatures, with 50% of cells surviving greater than 12 days in seawater at 10 °C, and more than 19 days at 4 °C. With one clam donor, living cells were observed for more than eight weeks at 4 °C. We also used qPCR of environmental DNA (eDNA) to detect the presence of MarBTN-specific DNA in the environment. We observed release of MarBTN-specific DNA into the water of laboratory aquaria containing highly MarBTN-diseased clams, and we detected MarBTN-specific DNA in seawater samples collected from MarBTN-endemic areas in Maine, although the copy numbers detected in environmental samples were much lower than those found in aquaria. Overall, these data show that MarBTN cells can survive well in seawater, and they are released into the water by diseased animals. These findings support the hypothesis that BTN is spread from animal-to-animal by free cells through seawater.

19.
J Virol ; 84(17): 8539-48, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20573819

RESUMEN

Infection of cells by herpes simplex virus type 1 (HSV-1) triggers host cell shutoff whereby mRNAs are degraded and cellular protein synthesis is diminished. However, virus protein translation continues because the translational apparatus in HSV-infected cells is maintained in an active state. Surprisingly, poly(A)-binding protein 1 (PABP1), a predominantly cytoplasmic protein that is required for efficient translation initiation, is partially relocated to the nucleus during HSV-1 infection. This relocalization occurred in a time-dependent manner with respect to virus infection. Since HSV-1 infection causes cell stress, we examined other cell stress inducers and found that oxidative stress similarly relocated PABP1. An examination of stress-induced kinases revealed similarities in HSV-1 infection and oxidative stress activation of JNK and p38 mitogen-activated protein (MAP) kinases. Importantly, PABP relocalization in infection was found to be independent of the viral protein ICP27. The depletion of PABP1 by small interfering RNA (siRNA) knockdown had no significant effect on viral replication or the expression of selected virus late proteins, suggesting that reduced levels of cytoplasmic PABP1 are tolerated during infection.


Asunto(s)
Núcleo Celular/metabolismo , Herpes Simple/metabolismo , Herpesvirus Humano 1/fisiología , Proteínas Inmediatas-Precoces/metabolismo , Proteína I de Unión a Poli(A)/metabolismo , Replicación Viral , Animales , Proteínas Portadoras , Núcleo Celular/genética , Chlorocebus aethiops , Regulación Viral de la Expresión Génica , Células HeLa , Herpes Simple/virología , Herpesvirus Humano 1/genética , Humanos , Proteínas Inmediatas-Precoces/genética , Estrés Oxidativo , Proteína I de Unión a Poli(A)/genética , Transporte de Proteínas , Células Vero
20.
Sex Transm Infect ; 87(2): 152-5, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21059841

RESUMEN

OBJECTIVE: To assess the effectiveness of electronic patient records (EPRs) in facilitating multiple, rapid measurements of treatment and partner notification (PN) outcomes for chlamydia and gonorrhoea. METHODS: In two sexual health clinics, the proportion of patients with chlamydia and gonorrhoea who had been treated within 4 weeks of diagnosis was measured, and also the proportion where at least one of their partners had been treated. These outcomes were measured monthly for 6 months, and changes in recording practice were instituted when necessary. RESULTS: It took 8 h to capture and analyse the data for 89 patients in month 1. The health advisers subsequently entered data into searchable fields to facilitate better data capture. As a result, by month 6 it took only 1.5 h to measure these outcomes using an electronic search. It had previously taken 2 days to perform the same analysis using paper records. In month 1, successful treatment was recorded in 26/27 (96%) patients with gonorrhoea and 57/61 (93%) with chlamydia, and there was successful PN for gonorrhoea and chlamydia patients in 19/27 (70%) and 39/61 (64%). By month 6, the recorded outcomes were 30/31 (97%) and 81/86 (94%), respectively, for successful treatment and 28/31 (90%) and 74/86 (86%) for successful PN, respectively. CONCLUSIONS: Frequent rapid clinical outcome monitoring is easily attained using EPRs as long as the data are entered into searchable fields. Treatment and PN success for chlamydia and gonorrhoea with this method are well above national targets, which may be attributable to both the use of EPRs and better data capture.


Asunto(s)
Infecciones por Chlamydia/terapia , Trazado de Contacto/métodos , Registros Electrónicos de Salud/normas , Gonorrea/terapia , Atención Ambulatoria , Humanos , Londres , Estudios Prospectivos , Sistemas Recordatorios , Parejas Sexuales , Resultado del Tratamiento
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