RESUMEN
Phosphorus (P) is typically considered to be the ultimate limiting nutrient for Earth's biosphere on geologic timescales. As P is monoisotopic, its sedimentary enrichment can provide some insights into how the marine P cycle has changed through time. A previous compilation of shale P enrichments argued for a significant change in P cycling during the Ediacaran Period (635-541 Ma). Here, using an updated P compilation-with more than twice the number of samples-we bolster the case that there was a significant transition in P cycling moving from the Precambrian into the Phanerozoic. However, our analysis suggests this state change may have occurred earlier than previously suggested. Specifically in the updated database, there is evidence for a transition ~35 million years before the onset of the Sturtian Snowball Earth glaciation in the Visingsö Group, potentially divorcing the climatic upheavals of the Neoproterozoic from changes in the Earth's P cycle. We attribute the transition in Earth's sedimentary P record to the onset of a more modern-like Earth system state characterized by less reducing marine conditions, higher marine P concentrations, and a greater predominance of eukaryotic organisms encompassing both primary producers and consumers. This view is consistent with organic biomarker evidence for a significant eukaryotic contribution to the preserved sedimentary organic matter in this succession and other contemporaneous Tonian marine sedimentary rocks. However, we stress that, even with an expanded dataset, we are likely far from pinpointing exactly when this transition occurred or whether Earth's history is characterized by a single or multiple transitions in the P cycle.
Asunto(s)
Sedimentos Geológicos , Fósforo , Sedimentos Geológicos/análisis , Eucariontes , MineralesRESUMEN
Despite developments in pharmacological treatments, chronic fatigue is an unresolved issue for most people with inflammatory arthritis that severely disrupts their personal and working lives. Fatigue in these patients is not strongly linked with peripheral disease activity but is associated with CNS-derived symptoms such as chronic pain, sleep disturbance, and depression. Therefore, a neurobiological basis should be considered when pursuing novel fatigue-specific therapeutics. In this Review, we focus on clinical imaging biomarkers that map candidate brain regions and are crucial in fatigue pathophysiology. We then evaluate neuromodulation techniques that could affect these candidate brain regions and are potential treatment strategies for fatigue in patients with inflammatory arthritis. We delineate work that is still required for neuroimaging and neuromodulation to eventually become part of a clinical pathway to treat and manage fatigue.
Asunto(s)
Artritis , Dolor Crónico , Humanos , Encéfalo/diagnóstico por imagen , Artritis/complicaciones , Dolor Crónico/etiología , Vías Clínicas , Mapeo EncefálicoRESUMEN
Peptide secondary metabolites are common in nature and have diverse pharmacologically-relevant functions, from antibiotics to cross-kingdom signaling. Here, we present a method to design large libraries of modified peptides in Escherichia coli and screen them in vivo to identify those that bind to a single target-of-interest. Constrained peptide scaffolds were produced using modified enzymes gleaned from microbial RiPP (ribosomally synthesized and post-translationally modified peptide) pathways and diversified to build large libraries. The binding of a RiPP to a protein target leads to the intein-catalyzed release of an RNA polymerase σ factor, which drives the expression of selectable markers. As a proof-of-concept, a selection was performed for binding to the SARS-CoV-2 Spike receptor binding domain. A 1625 Da constrained peptide (AMK-1057) was found that binds with similar affinity (990 ± 5 nM) as an ACE2-derived peptide. This demonstrates a generalizable method to identify constrained peptides that adhere to a single protein target, as a step towards "molecular glues" for therapeutics and diagnostics.
Asunto(s)
Antivirales/química , Antivirales/farmacología , Péptidos/química , Péptidos/farmacología , SARS-CoV-2/efectos de los fármacos , COVID-19/virología , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Humanos , Cinética , Modelos Moleculares , Péptidos/genética , Unión Proteica , SARS-CoV-2/genética , SARS-CoV-2/fisiología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Tratamiento Farmacológico de COVID-19RESUMEN
AIM: The aim was to evaluate the influence of a half day, hands-on, workshop on the detection and repair of obstetric anal sphincter injuries (OASIs). METHOD: Starting in February 2011, hands-on workshops for the diagnosis and repair of OASIs were delivered by trained urogynaecologists in departments of tertiary medical centres in Israel. The structure of the hands-on workshop resembles the workshop organized at the International Urogynecological Association annual conferences. Participants included medical staff, midwives and surgical residents from each medical centre. We collected data regarding the rate of OASIs, 1 year before and 1 year following the workshop, in 11 medical centres. The study population was composed of parturients with the following inclusion criteria: singleton pregnancy, vertex presentation and vaginal delivery. Pre-viable preterm gestations (< 24 weeks), birth weight < 500 g, stillborn, and those with major congenital anomalies, multifoetal pregnancies, breech presentations and caesarean deliveries were excluded from the analysis. RESULTS: In the reviewed centres, 70 663 (49.3%) women delivered prior to the workshop (pre-workshop group) and 72 616 (50.7%) women delivered following the workshop (post-workshop group). Third- or fourth-degree perineal tears occurred in 248 women (0.35%) before the workshop, and in 328 (0.45%) following the workshop, a significant increase of 28.7% (P = 0.002). The increase in diagnosis was significant also in women with third-degree tears alone, 226 women (0.32%) before the workshop and 298 (0.41%) following the workshop, an increase of 28.3% (P = 0.005). CONCLUSION: The detection rate of OASIs has significantly increased following the hands-on workshop. The implementation of such programmes is crucial for increasing awareness and detection rates of OASI following vaginal deliveries.
Asunto(s)
Laceraciones , Partería , Complicaciones del Trabajo de Parto , Canal Anal/lesiones , Parto Obstétrico , Femenino , Humanos , Recién Nacido , Israel/epidemiología , Laceraciones/diagnóstico , Laceraciones/epidemiología , Laceraciones/terapia , Complicaciones del Trabajo de Parto/diagnóstico , Complicaciones del Trabajo de Parto/epidemiología , Complicaciones del Trabajo de Parto/terapia , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Importance: Recommendations in the United States suggest limiting the number of patient records displayed in an electronic health record (EHR) to 1 at a time, although little evidence supports this recommendation. Objective: To assess the risk of wrong-patient orders in an EHR configuration limiting clinicians to 1 record vs allowing up to 4 records opened concurrently. Design, Setting, and Participants: This randomized clinical trial included 3356 clinicians at a large health system in New York and was conducted from October 2015 to April 2017 in emergency department, inpatient, and outpatient settings. Interventions: Clinicians were randomly assigned in a 1:1 ratio to an EHR configuration limiting to 1 patient record open at a time (restricted; n = 1669) or allowing up to 4 records open concurrently (unrestricted; n = 1687). Main Outcomes and Measures: The unit of analysis was the order session, a series of orders placed by a clinician for a single patient. The primary outcome was order sessions that included 1 or more wrong-patient orders identified by the Wrong-Patient Retract-and-Reorder measure (an electronic query that identifies orders placed for a patient, retracted, and then reordered shortly thereafter by the same clinician for a different patient). Results: Among the 3356 clinicians who were randomized (mean [SD] age, 43.1 [12.5] years; mean [SD] experience at study site, 6.5 [6.0] years; 1894 females [56.4%]), all provided order data and were included in the analysis. The study included 12â¯140â¯298 orders, in 4â¯486â¯631 order sessions, placed for 543â¯490 patients. There was no significant difference in wrong-patient order sessions per 100â¯000 in the restricted vs unrestricted group, respectively, overall (90.7 vs 88.0; odds ratio [OR], 1.03 [95% CI, 0.90-1.20]; P = .60) or in any setting (ED: 157.8 vs 161.3, OR, 1.00 [95% CI, 0.83-1.20], P = .96; inpatient: 185.6 vs 185.1, OR, 0.99 [95% CI, 0.89-1.11]; P = .86; or outpatient: 7.9 vs 8.2, OR, 0.94 [95% CI, 0.70-1.28], P = .71). The effect did not differ among settings (P for interaction = .99). In the unrestricted group overall, 66.2% of the order sessions were completed with 1 record open, including 34.5% of ED, 53.7% of inpatient, and 83.4% of outpatient order sessions. Conclusions and Relevance: A strategy that limited clinicians to 1 EHR patient record open compared with a strategy that allowed up to 4 records open concurrently did not reduce the proportion of wrong-patient order errors. However, clinicians in the unrestricted group placed most orders with a single record open, limiting the power of the study to determine whether reducing the number of records open when placing orders reduces the risk of wrong-patient order errors. Trial Registration: clinicaltrials.gov Identifier: NCT02876588.
Asunto(s)
Registros Electrónicos de Salud , Errores Médicos/estadística & datos numéricos , Centros Médicos Académicos , Adulto , Prestación Integrada de Atención de Salud , Femenino , Humanos , Masculino , Errores Médicos/prevención & control , Sistemas de Registros Médicos Computarizados/organización & administración , Persona de Mediana Edad , Comportamiento Multifuncional , Potencial Evento Adverso/estadística & datos numéricos , Seguridad del Paciente , Carga de TrabajoRESUMEN
INTRODUCTION: Golden retrievers are over-represented in cases of taurine-deficient dilated cardiomyopathy and recently a surge in cases has prompted further investigation. OBJECTIVE: To describe the clinical, dietary, and echocardiographic features in golden retrievers diagnosed with taurine deficiency and dilated cardiomyopathy, and to determine specific dietary associations. A second aim was to determine the whole blood taurine concentrations in a representative sample of healthy golden retrievers. ANIMALS: Twenty-four client-owned golden retrievers with documented taurine deficiency and dilated cardiomyopathy and 52 healthy client-owned golden retrievers. METHODS: In this multicenter prospective observational study, baseline and follow-up echocardiographic data, complete diet and medical histories, and whole blood, plasma, or serum taurine concentrations were obtained. Baseline and follow-up echocardiographic data were compared. Associations were evaluated between specific diets and taurine deficiency or congestive heart failure. The prevalence of low whole blood taurine concentrations in the healthy golden retrievers was calculated. RESULTS: Twenty-three of 24 dogs diagnosed with taurine deficiency and dilated cardiomyopathy were fed diets that were either grain-free, legume-rich, or a combination of these factors. None of these diets were feeding trial tested using Association of American Feed Control Officials (AAFCO) procedures. Twenty-three of 24 dogs had significant improvement in their echocardiographic parameters and normalization of taurine concentrations following diet change and taurine supplementation. Nine of 11 dogs diagnosed with congestive heart failure (CHF) had resolution of their congestion at follow-up with five no longer requiring diuretic therapy and four tolerating diuretic dose reduction by >50%. CONCLUSIONS: Certain diets and diet characteristics were associated with the development of taurine deficiency. Taurine deficiency and dilated cardiomyopathy in golden retrievers is likely multifactorial, including a combination of dietary, metabolic, and genetic factors.
Asunto(s)
Cardiomiopatía Dilatada/diagnóstico , Dieta/efectos adversos , Enfermedades de los Perros/diagnóstico , Taurina/metabolismo , Alimentación Animal/efectos adversos , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Cardiomiopatía Dilatada/etiología , Cardiomiopatía Dilatada/fisiopatología , Dieta/veterinaria , Enfermedades de los Perros/etiología , Enfermedades de los Perros/fisiopatología , Perros , Ecocardiografía , Grano Comestible/efectos adversos , Femenino , Corazón/diagnóstico por imagen , Corazón/fisiopatología , Masculino , Taurina/deficiencia , Taurina/genéticaRESUMEN
INTRODUCTION AND AIM: We sought to identify independent risk factors for cirrhosis in HFE p.C282Y homozygotes in a cross-sectional study. MATERIAL AND METHODS: We evaluated 368 p.C282Y homozygotes who underwent liver biopsy and compared characteristics of those with and without cirrhosis. We performed multivariable logistic regression on cirrhosis with: age; sex; race/ethnicity; diabetes; blood pints/units donated voluntarily; erythrocyte pints/units received; iron supplement use; alcohol intake, g/d; body mass index, kg/m2; swollen/tender 2nd/3rd metacarpophalangeal joints; elevated alanine aminotransferase; elevated aspartate aminotransferase; steatosis/fatty liver; iron removed by phlebotomy, g; and GNPAT p.D519G positivity. RESULTS: Mean age of 368 participants (73.6% men) was 47 ± 13 (standard deviation) y. Cirrhosis was diagnosed in 86 participants (23.4%). Participants with cirrhosis had significantly greater mean age, proportion of men, diabetes prevalence, mean daily alcohol intake, prevalence of swollen/ tender 2nd/3rd metacarpophalangeal joints, mean serum ferritin, elevated alanine aminotransferase, elevated aspartate aminotransferase, and mean iron removed; and significantly fewer mean blood pints/units donated. GNPAT p.D519G positivity was detected in 82 of 188 participants (43.6%). In a multivariable model for cirrhosis, there were four significant positive associations: age (10-y intervals) (odds ratio 2.2 [95% confidence interval 1.5, 3.3]); diabetes (3.3; [1.1, 9.7]); alcohol intake (14 g alcohol drinks/d) (1.5 [1.2, 1.8]); and iron removed, g (1.3 [1.2, 1.4]). There was no statistical evidence of two-way interactions between these variables. CONCLUSION: In conclusion, cirrhosis in HFE p.C282Y homozygotes is significantly associated with age, diabetes, daily alcohol intake, and iron removed by phlebotomy, taking into account the effect of other variables.
Asunto(s)
Proteína de la Hemocromatosis/genética , Hemocromatosis/genética , Homocigoto , Cirrosis Hepática/genética , Mutación , Aciltransferasas/genética , Adulto , Factores de Edad , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Australia/epidemiología , Comorbilidad , Estudios Transversales , Diabetes Mellitus/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Hemocromatosis/diagnóstico , Hemocromatosis/epidemiología , Hemocromatosis/terapia , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Fenotipo , Flebotomía , Polimorfismo de Nucleótido Simple , Prevalencia , Medición de Riesgo , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Two-thirds of adults worldwide will experience low back pain at some point in their life. In the following case series, we present four patients with sacroiliac (SI) joint instability and severe chronic low back pain, which was refractory to other treatment modalities. OBJECTIVE: We investigated the efficacy of platelet-rich plasma (PRP) injections, a novel orthobiologic therapy, for reducing SI joint pain, improving quality of life, and maintaining a clinical effect. METHODS: Short-form McGill Pain Questionnaire (SFM), Numeric Rating Scale (NRS), and Oswestry Low Back Pain and Disability Index were used for evaluation of treatment at pretreatment, 12-months and 48-months after treatment. RESULTS: At follow-up 12-months post-treatment, pooled data from all patients reported a marked improvement in joint stability, a statistically significant reduction in pain, and improvement in quality of life. The clinical benefits of PRP were still significant at 4-years post-treatment. CONCLUSIONS: Platelet-rich plasma therapy exhibits clinical usefulness in both pain reduction and for functional improvement in patients with chronic SI joint pain. The improvement in joint stability and low back pain was maintained at 1- and 4-years post-treatment.
Asunto(s)
Dolor de la Región Lumbar/terapia , Plasma Rico en Plaquetas , Articulación Sacroiliaca/diagnóstico por imagen , Adulto , Anciano , Femenino , Humanos , Inyecciones Intraarticulares , Dolor de la Región Lumbar/diagnóstico por imagen , Persona de Mediana Edad , Dimensión del Dolor , Calidad de Vida , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
BACKGROUND: GNPAT p.D519G positivity is significantly increased in HFE p.C282Y homozygotes with markedly increased iron stores. We sought to determine associations of p.D519G and iron-related variables with iron stores in p.C282Y homozygotes. METHODS: We defined markedly increased iron stores as serum ferritin >2247pmol/L (>1000µg/L) and either hepatic iron >236µmol/g dry weight or iron >10g by induction phlebotomy (men and women). We defined normal or mildly elevated iron stores as serum ferritin <674.1pmol/L (<300µg/L) or either age≥40y with iron ≤2.5g iron by induction phlebotomy or age≥50y with ≤3.0g iron by induction phlebotomy (men only). We compared participant subgroups using univariate methods. Using multivariable logistic regression, we evaluated associations of markedly increased iron stores with these variables: age; iron supplement use (dichotomous); whole blood units donated; erythrocyte units received as transfusion; daily alcohol consumption, g; and p.D519G positivity (heterozygosity or homozygosity). RESULTS: The mean age of 56 participants (94.6% men) was 55±10 (SD) y; 41 had markedly increased iron stores. Prevalences of swollen/tender 2nd/3rd metacarpophalangeal joints and elevated aspartate or alanine aminotransferase were significantly greater in participants with markedly increased iron stores. Only participants with markedly increased iron stores had cirrhosis. In multivariable analyses, p.D519G positivity was the only exposure variable significantly associated with markedly increased iron stores (odds ratio 9.9, 95% CI [1.6, 60.3], p=0.0126). CONCLUSIONS: GNPAT p.D519G is strongly associated with markedly increased iron stores in p.C282Y homozygotes after correction for age, iron-related variables, and alcohol consumption.
Asunto(s)
Aciltransferasas/genética , Proteína de la Hemocromatosis/genética , Hierro/metabolismo , Mutación Missense , Aciltransferasas/metabolismo , Adulto , Factores de Edad , Anciano , Consumo de Bebidas Alcohólicas , Femenino , Proteína de la Hemocromatosis/metabolismo , Homocigoto , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The hearing sensitivity of 18 free-ranging and 10 captive harbour seals (Phoca vitulina) to aerial sounds was measured in the presence of typical environmental noise through auditory brainstem response measurements. A focus was put on the comparative hearing sensitivity at low frequencies. Low- and mid-frequency thresholds appeared to be elevated in both captive and free-ranging seals, but this is likely due to masking effects and limitations of the methodology used. The data also showed individual variability in hearing sensitivity with probable age-related hearing loss found in two old harbour seals. These results suggest that the acoustic sensitivity of free-ranging animals was not negatively affected by the soundscape they experienced in the wild.
Asunto(s)
Animales Salvajes/fisiología , Animales de Zoológico/fisiología , Percepción Auditiva/fisiología , Umbral Auditivo/fisiología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Phoca/fisiología , Estimulación Acústica , Envejecimiento/fisiología , Animales , Audiometría , Femenino , Pérdida Auditiva/fisiopatología , Masculino , Phoca/crecimiento & desarrollo , Análisis de RegresiónRESUMEN
Mycobacteria in complete Freund's adjuvant (CFA) are an essential component of immunization protocols in a number of autoimmune disease animal models including experimental autoimmune encephalomyelitis and uveoretinitis (EAE and EAU, respectively). We determined the role in EAU of two C-type lectin receptors on myeloid cells that recognize and respond to mycobacteria. Using receptor-specific antibodies and knockout mice, we demonstrated for the first time that the macrophage mannose receptor delays disease development but does not affect severity. In contrast, dectin-1 is critically involved in the development of CFA-mediated EAU. Disease severity is reduced in dectin-1 knockout mice and antibody blockade of dectin-1 during the induction, but not the effector phase, prevents EAU development. Significantly, similar blockade of dectin-1 in vivo has no effect in non-CFA-mediated, spontaneously induced or adoptive transfer models of EAU. Thus dectin-1 plays a critical role in the ability of complete Freund's adjuvant to induce EAU in mice.
Asunto(s)
Enfermedades Autoinmunes/metabolismo , Lectinas Tipo C/metabolismo , Receptores de Reconocimiento de Patrones/metabolismo , Retinitis/metabolismo , Uveítis/metabolismo , Animales , Anticuerpos Bloqueadores/farmacología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Quimiocinas/metabolismo , Modelos Animales de Enfermedad , Adyuvante de Freund/inmunología , Humanos , Inmunización , Mediadores de Inflamación/metabolismo , Lectinas Tipo C/deficiencia , Lectinas Tipo C/inmunología , Ganglios Linfáticos/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Reconocimiento de Patrones/deficiencia , Receptores de Reconocimiento de Patrones/inmunología , Retina/efectos de los fármacos , Retina/metabolismo , Retina/patología , Retinitis/inmunología , Retinitis/patología , Proteínas de Unión al Retinol/metabolismo , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Th17/efectos de los fármacos , Células Th17/inmunología , Factores de Tiempo , Uveítis/inmunología , Uveítis/patologíaRESUMEN
We sought to examine the relationship between elevated transferrin saturation (TS) and measures of health status (telomere length and patient-reported health-related quality of life) to assess whether elevated TS is associated with negative patient outcomes beyond increased risk for morbidity and mortality, using a cross-sectional analysis of the Hemochromatosis and Iron Overload Screening Study supplemented with assays for leukocyte telomere length in adults ≥25 years old (n = 669). Among individuals with elevated TS (≥45 % for women and ≥50 % for men), who also had a usual source of care, only 5.2 % reported ever being told by a doctor that they had an elevated iron condition. In a fully adjusted general linear regression model controlling for demographic characteristics as well as health conditions associated with iron overload, elevated TS versus non-elevated TS was associated with worse general health status (60.4 vs. 63.8, P < 0.05), mental health status (76.5 vs. 82.2, P < 0.0001) and shorter telomere length (241.4 vs. 261.3, P < 0.05). Increased surveillance of elevated TS may be in order as elevated TS is associated with decreased health status and very few patients with elevated TS are aware of their condition.
Asunto(s)
Calidad de Vida , Telómero/metabolismo , Transferrina/análisis , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Telómero/genética , Transferrina/metabolismoRESUMEN
BACKGROUND: Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes. METHODS/DESIGN: A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates. DISCUSSION: Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic. TRIAL REGISTRATION NUMBER: ISRCTN45190901.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , Fluorobencenos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Gripe Humana/tratamiento farmacológico , Pirimidinas/uso terapéutico , Proyectos de Investigación , Sulfonamidas/uso terapéutico , Enfermedad Aguda , Argentina , Australia , Canadá , Conducta Cooperativa , Cuidados Críticos , Enfermedad Crítica , Quimioterapia Combinada , Estudios de Factibilidad , Humanos , Gripe Humana/diagnóstico , Gripe Humana/virología , Consentimiento Informado , México , Nueva Zelanda , Selección de Paciente , Proyectos Piloto , Respiración Artificial , Rosuvastatina Cálcica , Arabia Saudita , Resultado del TratamientoRESUMEN
PURPOSE: Combinations of drugs and laboratory values ("drug-laboratory pairs") that represent practical high-priority targets for potential use in a daily asynchronous inpatient clinical decision-support (CDS) alert report were identified. METHODS: A list of 654 drug-laboratory pairs compiled through a literature review was evaluated by a multidisciplinary expert panel in a modified Delphi procedure. After initial evaluation to narrow the list to 89 drug-laboratory pairs, panelists used Likert scales to rate the remaining pairs on six dimensions (frequency of alert, likelihood of harm, severity of harm, preventability, ameliorability, and global impression of usefulness) in Delphi survey rounds until consensus emerged. Final selection of pairs for potential use as CDS tools was based on global-impression-of-usefulness scores. Correlations between impression of usefulness and other evaluative dimensions were determined. RESULTS: The Delphi process yielded a final list of 24 high-priority drug-laboratory pairs. The highest-ranked pairs were heparin- low platelet count, potassium supplement- high serum potassium, angiotensin-converting-enzyme inhibitor-high serum potassium, and heparin-positive heparin platelet factor 4 antibody test. Medications on the final list included nine anticoagulants, six cardiologic agents, four antimicrobials, and two electrolytes. Most of the selected drug-laboratory pairs related to renal function, serum potassium levels, hematologic results, or pregnancy. Panelists' impression of usefulness was significantly correlated with severity-of-harm ratings (p < 0.0001). CONCLUSION: Expert review of drug- laboratory value pairs for potential inclusion in an asynchronous monitoring program yielded 24 high-priority and practical pairs for monitoring. About 25% of the pairs had not been the focus of previous laboratory-pharmacy CDS at the study panelists' home institutions.
Asunto(s)
Sistemas de Apoyo a Decisiones Clínicas , Monitoreo de Drogas/métodos , Errores de Medicación/prevención & control , Pautas de la Práctica en Medicina/normas , Adulto , Técnica Delphi , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Preparaciones Farmacéuticas/administración & dosificaciónRESUMEN
Five horses were presented with signs of myopathy along with systemic malaise, hyperfibrinogenemia, hyperphosphatemia, and an elevated calcium phosphorus product (Ca*P). Postmortem findings were consistent with systemic calcinosis, a syndrome of calcium deposition in the tissue of organs including lungs, kidneys, muscle, and heart that has not been previously described in horses.
Asunto(s)
Calcinosis/veterinaria , Enfermedades de los Caballos/diagnóstico , Animales , Calcinosis/sangre , Calcinosis/diagnóstico , Calcifilaxia/sangre , Calcifilaxia/diagnóstico , Calcifilaxia/veterinaria , Calcio/sangre , Resultado Fatal , Enfermedades de los Caballos/sangre , Caballos , Masculino , Fósforo/sangreRESUMEN
Routine actions are commonly assumed to be controlled by hierarchically organized processes and representations. In the domain of typing theories, word-level information is assumed to activate the constituent keystrokes required to type each letter in a word. We tested this assumption directly using a novel single-letter probe technique. Subjects were primed with a visual or auditory word or a visually presented random consonant string and then probed to type a single letter from the prime or another randomly selected letter. Relative to randomly selected letters, probe responses were speeded for first, middle, and last letters contained in visual and auditory word primes but not for middle and last letters contained in random consonant primes. This suggests that word-level information causes parallel activation of constituent keystrokes, consistent with hierarchical processing. The role of hierarchical processing in typing and routine action is discussed.
Asunto(s)
Función Ejecutiva/fisiología , Dedos/fisiología , Reconocimiento Visual de Modelos , Desempeño Psicomotor/fisiología , Vocabulario , Estimulación Acústica/métodos , Análisis de Varianza , Femenino , Humanos , Masculino , Estimulación Luminosa/métodos , Tiempo de Reacción/fisiología , Lectura , Detección de Señal Psicológica , EstudiantesRESUMEN
OBJECTIVE: The aim of this case series study was to investigate and report on patients with neuropathic pain who responded to treatment with omega-3 fatty acids. METHODS: Methods: Five patients with different underlying diagnoses including cervical radiculopathy, thoracic outlet syndrome, fibromyalgia, carpal tunnel syndrome, burn injury were treated with high oral doses of omega 3 fish oil (varying from 2400-7200 mg/day of EPA-DHA). Outcome measures were obtained pretreatment and posttreatment. These included validated surveys (short-form McGill Pain questionnaire, DN4 neuropathic pain scale, Pain Detect Questionnaire), objective clinical tools (Jamar grip strength, Lafayette dynamometry, tender point algometry) and EMG Nerve Conduction studies. RESULTS: These patients had clinically significant pain reduction, improved function as documented with both subjective and objective outcome measures up to as much as 19 months after treatment initiation. No serious adverse effects were reported. CONCLUSIONS: This first-ever reported case series suggests that omega-3 fatty acids may be of benefit in the management of patients with neuropathic pain. Further investigations with randomized controlled trials in a more specific neuropathic pain population would be warranted.
Asunto(s)
Ácidos Grasos Omega-3/administración & dosificación , Neuralgia/tratamiento farmacológico , Administración Oral , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodosRESUMEN
The Neoproterozoic era (1,000-542 Myr ago) was an era of climatic extremes and biological evolutionary developments culminating in the emergence of animals (Metazoa) and new ecosystems. Here we show that abundant sedimentary 24-isopropylcholestanes, the hydrocarbon remains of C(30) sterols produced by marine demosponges, record the presence of Metazoa in the geological record before the end of the Marinoan glaciation ( approximately 635 Myr ago). These sterane biomarkers are abundant in all formations of the Huqf Supergroup, South Oman Salt Basin, and, based on a new high-precision geochronology, constitute a continuous 100-Myr-long chemical fossil record of demosponges through the terminal Neoproterozoic and into the Early Cambrian epoch. The demosponge steranes occur in strata that underlie the Marinoan cap carbonate (>635 Myr ago). They currently represent the oldest evidence for animals in the fossil record, and are evidence for animals pre-dating the termination of the Marinoan glaciation. This suggests that shallow shelf waters in some late Cryogenian ocean basins (>635 Myr ago) contained dissolved oxygen in concentrations sufficient to support basal metazoan life at least 100 Myr before the rapid diversification of bilaterians during the Cambrian explosion. Biomarker analysis has yet to reveal any convincing evidence for ancient sponges pre-dating the first globally extensive Neoproterozoic glacial episode (the Sturtian, approximately 713 Myr ago in Oman).
Asunto(s)
Evolución Biológica , Colestanos/análisis , Colestanos/química , Fósiles , Sedimentos Geológicos/química , Poríferos/fisiología , Animales , Arabia , Biomarcadores/análisis , Biomarcadores/química , Colestanos/aislamiento & purificación , Cromatografía de Gases y Espectrometría de Masas , Historia Antigua , Hidrocarburos/análisis , Hidrocarburos/química , Cubierta de Hielo , Océanos y Mares , Oxígeno/análisis , Agua de Mar/químicaRESUMEN
This study assessed how the palatability of leaves of different age classes (young, intermediate and older) of Eucalyptus nitens seedlings varied with plant nutrient status, based on captive feeding trials with two mammalian herbivores, red-bellied pademelons (Thylogale billardierii), and common brushtail possums (Trichosurus vulpecula). Seedlings were grown under three nutrient treatments (low, medium and high), and we determined how palatability was related to chemical and physical characteristics of the leaves. Pademelons ate more older leaves than young and intermediate leaves for all treatments. This pattern was best explained by sideroxylonals (formylated phloroglucinol compounds known to deter herbivory by other marsupials), and/or essential oil compounds that were present in lower concentrations in older leaves. In the low-nutrient treatment, possums also ate more of the older leaves. However, in the medium- and high-nutrient treatments, possums ate more intermediate leaves than older leaves and showed a behavioural preference for young leaves (consuming younger leaves first) over intermediate and older leaves, in spite of high levels of sideroxylonals and essential oils. The young leaves did, however, have the highest nitrogen concentration of all the leaf age classes. Thus, either sideroxylonals and essential oils provided little or no deterrent to possums, or the deterrent was outweighed by other factors such as high nitrogen. This study indicates that mammalian herbivores show different levels of relative use and damage to leaf age classes at varying levels of plant nutrient status and, therefore, their impact on plant fitness may vary with environment.
Asunto(s)
Eucalyptus , Conducta Alimentaria/fisiología , Macropodidae/fisiología , Hojas de la Planta/química , Plantones/química , Suelo/análisis , Trichosurus/fisiología , Animales , Modelos Lineales , Floroglucinol/análisis , Hojas de la Planta/anatomía & histología , Aceites de Plantas/análisis , Tasmania , Grabación en VideoRESUMEN
The disappearance of iron formations from the geological record approximately 1.8 billion years (Gyr) ago was the consequence of rising oxygen levels in the atmosphere starting 2.45-2.32 Gyr ago. It marks the end of a 2.5-Gyr period dominated by anoxic and iron-rich deep oceans. However, despite rising oxygen levels and a concomitant increase in marine sulphate concentration, related to enhanced sulphide oxidation during continental weathering, the chemistry of the oceans in the following mid-Proterozoic interval (approximately 1.8-0.8 Gyr ago) probably did not yet resemble our oxygen-rich modern oceans. Recent data indicate that marine oxygen and sulphate concentrations may have remained well below current levels during this period, with one model indicating that anoxic and sulphidic marine basins were widespread, and perhaps even globally distributed. Here we present hydrocarbon biomarkers (molecular fossils) from a 1.64-Gyr-old basin in northern Australia, revealing the ecological structure of mid-Proterozoic marine communities. The biomarkers signify a marine basin with anoxic, sulphidic, sulphate-poor and permanently stratified deep waters, hostile to eukaryotic algae. Phototrophic purple sulphur bacteria (Chromatiaceae) were detected in the geological record based on the new carotenoid biomarker okenane, and they seem to have co-existed with communities of green sulphur bacteria (Chlorobiaceae). Collectively, the biomarkers support mounting evidence for a long-lasting Proterozoic world in which oxygen levels remained well below modern levels.