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1.
Appl Opt ; 62(8): C30-C37, 2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-37133054

RESUMEN

In recent years, an unconventional excitation of trivalent neodymium ions (N d 3+) at 1064 nm, not resonant with ground-state transitions, has been investigated with the unprecedented demonstration of a photon-avalanche-like (PA-like) mechanism, in which the temperature increase plays a fundamental role. As a proof-of-concept, N d A l 3(B O 3)4 particles were used. A consequence of the PA-like mechanism is the absorption enhancement of excitation photons providing light emission at a broad range covering the visible and near-infrared spectra. In the first study, the temperature increase was due to intrinsic nonradiative relaxations from the N d 3+ and the PA-like mechanism ensued at a given excitation power threshold (P t h ). Subsequently, an external heating source was used to trigger the PA-like mechanism while keeping the excitation power below P t h at room temperature. Here, we demonstrate the switching on of the PA-like mechanism by an auxiliary beam at 808 nm, which is in resonance with the N d 3+ ground-state transition 4 I 9/2→{4 F 5/2,2 H 9/2}. It comprises the first, to the best of our knowledge, demonstration of an optical switched PA, and the underlying physical mechanism is the additional heating of the particles due to the phonon emissions from the N d 3+ relaxation pathways when exciting at 808 nm. The present results have potential applications in controlled heating and remote temperature sensing.

2.
Molecules ; 28(11)2023 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-37298988

RESUMEN

Chagas disease (CD) is one of the main neglected tropical diseases that promote relevant socioeconomic impacts in several countries. The therapeutic options for the treatment of CD are limited, and parasite resistance has been reported. Piplartine is a phenylpropanoid imide that has diverse biological activities, including trypanocidal action. Thus, the objective of the present work was to prepare a collection of thirteen esters analogous to piplartine (1-13) and evaluate their trypanocidal activity against Trypanosoma cruzi. Of the tested analogues, compound 11 ((E)-furan-2-ylmethyl 3-(3,4,5-trimethoxyphenyl)acrylate) showed good activity with IC50 values = 28.21 ± 5.34 µM and 47.02 ± 8.70 µM, against the epimastigote and trypomastigote forms, respectively. In addition, it showed a high rate of selectivity to the parasite. The trypanocidal mechanism of action occurs through the induction of oxidative stress and mitochondrial damage. In addition, scanning electron microscopy showed the formation of pores and leakage of cytoplasmic content. Molecular docking indicated that 11 probably produces a trypanocidal effect through a multi-target mechanism, including affinity with proteins CRK1, MPK13, GSK3B, AKR, UCE-1, and UCE-2, which are important for the survival of the parasite. Therefore, the results suggest chemical characteristics that can serve for the development of new trypanocidal prototypes for researching drugs against Chagas disease.


Asunto(s)
Enfermedad de Chagas , Tripanocidas , Trypanosoma cruzi , Humanos , Tripanocidas/química , Simulación del Acoplamiento Molecular , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitología , Estrés Oxidativo
3.
N Engl J Med ; 381(26): 2529-2540, 2019 12 26.
Artículo en Inglés | MEDLINE | ID: mdl-31826336

RESUMEN

BACKGROUND: Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality. RESULTS: A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P = 0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality. CONCLUSIONS: Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. (Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314.).


Asunto(s)
Colecalciferol/administración & dosificación , Enfermedad Crítica/terapia , Deficiencia de Vitamina D/tratamiento farmacológico , Vitaminas/administración & dosificación , Adulto , Colecalciferol/efectos adversos , Enfermedad Crítica/mortalidad , Método Doble Ciego , Femenino , Humanos , Estimación de Kaplan-Meier , Tiempo de Internación , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Insuficiencia del Tratamiento , Vitamina D/análogos & derivados , Vitamina D/sangre , Vitaminas/efectos adversos
4.
Crit Care Med ; 49(10): 1651-1663, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-33938716

RESUMEN

OBJECTIVES: Host gene expression signatures discriminate bacterial and viral infection but have not been translated to a clinical test platform. This study enrolled an independent cohort of patients to describe and validate a first-in-class host response bacterial/viral test. DESIGN: Subjects were recruited from 2006 to 2016. Enrollment blood samples were collected in an RNA preservative and banked for later testing. The reference standard was an expert panel clinical adjudication, which was blinded to gene expression and procalcitonin results. SETTING: Four U.S. emergency departments. PATIENTS: Six-hundred twenty-three subjects with acute respiratory illness or suspected sepsis. INTERVENTIONS: Forty-five-transcript signature measured on the BioFire FilmArray System (BioFire Diagnostics, Salt Lake City, UT) in ~45 minutes. MEASUREMENTS AND MAIN RESULTS: Host response bacterial/viral test performance characteristics were evaluated in 623 participants (mean age 46 yr; 45% male) with bacterial infection, viral infection, coinfection, or noninfectious illness. Performance of the host response bacterial/viral test was compared with procalcitonin. The test provided independent probabilities of bacterial and viral infection in ~45 minutes. In the 213-subject training cohort, the host response bacterial/viral test had an area under the curve for bacterial infection of 0.90 (95% CI, 0.84-0.94) and 0.92 (95% CI, 0.87-0.95) for viral infection. Independent validation in 209 subjects revealed similar performance with an area under the curve of 0.85 (95% CI, 0.78-0.90) for bacterial infection and 0.91 (95% CI, 0.85-0.94) for viral infection. The test had 80.1% (95% CI, 73.7-85.4%) average weighted accuracy for bacterial infection and 86.8% (95% CI, 81.8-90.8%) for viral infection in this validation cohort. This was significantly better than 68.7% (95% CI, 62.4-75.4%) observed for procalcitonin (p < 0.001). An additional cohort of 201 subjects with indeterminate phenotypes (coinfection or microbiology-negative infections) revealed similar performance. CONCLUSIONS: The host response bacterial/viral measured using the BioFire System rapidly and accurately discriminated bacterial and viral infection better than procalcitonin, which can help support more appropriate antibiotic use.


Asunto(s)
Infecciones Bacterianas/diagnóstico , Técnicas de Laboratorio Clínico/normas , Transcriptoma , Virosis/diagnóstico , Adulto , Infecciones Bacterianas/genética , Biomarcadores/análisis , Biomarcadores/sangre , Técnicas de Laboratorio Clínico/métodos , Técnicas de Laboratorio Clínico/estadística & datos numéricos , Servicio de Urgencia en Hospital/organización & administración , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Virosis/genética
5.
BMC Health Serv Res ; 21(1): 498, 2021 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-34030696

RESUMEN

BACKGROUND: Health Management Information System (HMIS) is a set of data regularly collected at health care facilities to meet the needs of statistics on health services. This study aimed to determine the utilisation of HMIS data and factors influencing the health system's performance at the district and primary health care facility levels in Tanzania. METHODS: This cross-sectional study was carried out in 11 districts and involved 115 health care facilities in Tanzania. Data were collected using a semi-structured questionnaire administered to health workers at facility and district levels and documented using an observational checklist. Thematic content analysis approach was used to synthesise and triangulate the responses and observations to extract essential information. RESULTS: A total of 93 healthcare facility workers and 13 district officials were interviewed. About two-thirds (60%) of the facility respondents reported using the HMIS data, while only five out of 13 district respondents (38.5%) reported analysing HMIS data routinely. The HMIS data were mainly used for comparing performance in terms of services coverage (53%), monitoring of disease trends over time (50%), and providing evidence for community health education and promotion programmes (55%). The majority (41.4%) of the facility's personnel had not received any training on data management related to HMIS during the past 12 months prior to the survey. Less than half (42%) of the health facilities had received supervisory visits from the district office 3 months before this assessment. Nine district respondents (69.2%) reported systematically receiving feedback on the quality of their reports monthly and quarterly from higher authorities. Patient load was described to affect staff performance on data collection and management frequently. CONCLUSION: Inadequate analysis and poor data utilisation practices were common in most districts and health facilities in Tanzania. Inadequate human and financial resources, lack of incentives and supervision, and lack of standard operating procedures on data management were the significant challenges affecting the HMIS performance in Tanzania.


Asunto(s)
Sistemas de Información en Salud , Sistemas de Información Administrativa , Estudios Transversales , Instituciones de Salud , Humanos , Tanzanía
6.
J Clin Microbiol ; 58(9)2020 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-32641399

RESUMEN

Blood culture (BC) often fails to detect bloodstream microorganisms in sepsis. However, molecular diagnostics hold great potential. The molecular method PCR/electrospray ionization-mass spectrometry (PCR/ESI-MS) can detect DNA from hundreds of different microorganisms in whole blood. The aim of the present study was to evaluate the performance of this method in a multicenter study including 16 teaching hospitals in the United States (n = 13) and Europe (n = 3). First, on testing of 2,754 contrived whole blood samples, with or without spiked microorganisms, PCR/ESI-MS produced 99.1% true-positive and 97.2% true-negative results. Second, among 1,460 patients with suspected sepsis (sepsis-2 definition), BC and PCR/ESI-MS on whole blood were positive in 14.6% and 25.6% of cases, respectively, with the following result combinations: BC positive and PCR/ESI-MS negative, 4.3%; BC positive and PCR/ESI-MS positive, 10.3%; BC negative and PCR/ESI-MS positive, 15.3%; and BC negative and PCR/ESI-MS negative, 70.1%. Compared with BC, PCR/ESI-MS showed the following sensitivities (coagulase-negative staphylococci not included): Gram-positive bacteria, 58%; Gram-negative bacteria, 78%; and Candida species, 83%. The specificities were >94% for all individual species. Patients who had received prior antimicrobial medications (n = 603) had significantly higher PCR/ESI-MS positivity rates than patients without prior antimicrobial treatment-31% versus 22% (P < 0.0001)-with pronounced differences for Gram-negative bacteria and Candida species. In conclusion, PCR/ESI-MS showed excellent performance on contrived samples. On clinical samples, it showed high specificities, moderately high sensitivities for Gram-negative bacteria and Candida species, and elevated positivity rates during antimicrobial treatment. These promising results encourage further development of molecular diagnostics to be used with whole blood for detection of bloodstream microorganisms in sepsis.


Asunto(s)
Sepsis , Espectrometría de Masa por Ionización de Electrospray , Cultivo de Sangre , Europa (Continente) , Humanos , Reacción en Cadena de la Polimerasa , Sepsis/diagnóstico
7.
Biomarkers ; 25(5): 391-396, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32421363

RESUMEN

Objective: We previously demonstrated that plasma levels of F-actin and Thymosin Beta 4 differs among patients with septic shock, non-infectious systemic inflammatory syndrome and healthy controls and may serve as biomarkers for the diagnosis of sepsis. The current study aims to determine if these proteins are associated with or predictive of illness severity in patients at risk for sepsis in the Emergency Department (ED).Methods: Prospective, biomarker study enrolling patients (>18 years) who met the Shock Precautions on Triage Sepsis rule placing them at-risk for sepsis.Results: In this study of 203 ED patients, F-actin plasma levels had a linear trend of increase when the quick Sequential Organ Failure Assessment (qSOFA) score increased. F-actin was also increased in patients who were admitted to the Intensive Care Unit (ICU) from the ED, and in those with positive urine cultures. Thymosin Beta 4 was not associated with or predictive of any significant outcome measures.Conclusion: Increased levels of plasma F-actin measured in the ED were associated with incremental illness severity as measured by the qSOFA score and need for ICU admission. F-actin may have utility in risk stratification of undifferentiated patients in the ED presenting with signs and symptoms of sepsis.


Asunto(s)
Actinas/sangre , Inflamación/sangre , Sepsis/sangre , Choque Séptico/sangre , Timosina/sangre , Adulto , Anciano , Infecciones Bacterianas/sangre , Infecciones Bacterianas/mortalidad , Infecciones Bacterianas/patología , Biomarcadores/sangre , Servicio de Urgencia en Hospital , Femenino , Hospitalización , Humanos , Inflamación/microbiología , Inflamación/patología , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Enfermedades no Transmisibles/epidemiología , Puntuaciones en la Disfunción de Órganos , Pronóstico , Factores de Riesgo , Sepsis/microbiología , Sepsis/patología , Choque Séptico/microbiología , Choque Séptico/patología
8.
BMC Med Inform Decis Mak ; 20(1): 340, 2020 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-33334323

RESUMEN

BACKGROUND: Effective planning for disease prevention and control requires accurate, adequately-analysed, interpreted and communicated data. In recent years, efforts have been put in strengthening health management information systems (HMIS) in Sub-Saharan Africa to improve data accessibility to decision-makers. This study assessed the quality of routine HMIS data at primary healthcare facility (HF) and district levels in Tanzania. METHODS: This cross-sectional study involved reviews of documents, information systems and databases, and collection of primary data from facility-level registers, tally sheets and monthly summary reports. Thirty-four indicators from Outpatient, Inpatient, Antenatal care, Family Planning, Post-natal care, Labour and Delivery, and Provider-Initiated Testing and Counselling service areas were assessed. Indicator records were tracked and compared across the process of data collection, compilation and submission to the district office. Copies of monthly report forms submitted by facilities to the district were also reviewed. The availability and utilization of HMIS tools were assessed, while completeness and data accuracy levels were quantified for each phase of the reporting system. RESULTS: A total of 115 HFs (including hospitals, health centres, dispensaries) in 11 districts were involved. Registers (availability rate = 91.1%; interquartile range (IQR) 66.7-100%) and report forms (86.9%; IQR 62.2-100%) were the most utilized tools. There was a limited use of tally-sheets (77.8%; IQR 35.6-100%). Tools availability at the dispensary was 91.1%, health centre 82.2% and hospital 77.8%, and was low in urban districts. The availability rate at the district level was 65% (IQR 48-75%). Wrongly filled or empty cells in registers and poor adherence to the coding procedures were observed. Reports were highly over-represented in comparison to registers' records, with large differences observed at the HF phase of the reporting system. The OPD and IPD areas indicated the highest levels of mismatch between data source and district office. Indicators with large number of clients, multiple variables, disease categorization, or those linked with dispensing medicine performed poorly. CONCLUSION: There are high variations in the tool utilisation and data accuracy at facility and district levels. The routine HMIS is weak and data at district level inaccurately reflects what is available at the source. These results highlight the need to design tailored and inter-service strategies for improving data quality.


Asunto(s)
Exactitud de los Datos , Recolección de Datos/normas , Sistemas de Información Administrativa , Atención Primaria de Salud/normas , Estudios Transversales , Femenino , Humanos , Masculino , Atención Primaria de Salud/organización & administración , Tanzanía
9.
Curr Ther Res Clin Exp ; 93: 100604, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32963641

RESUMEN

BACKGROUND: Recombinant human hyaluronidase PH20 (rHuPH20) is used in subcutaneous formulations (eg, RITUXAN HYCELA [rituximab and hyaluronidase human], HERCEPTIN HYLECTA [trastuzumab and hyaluronidase-oysk], PHESGO [pertuzumab/trastuzumab/hyaluronidase-zzxf], and Darzalex FASPRO [daratumumab and hyaluronidase-fihj]) to increase the dispersion and absorption of coadministered therapeutics. Although unlikely, subcutaneous products that include rHuPH20 could be mistaken for the intravenous formulation of the corresponding drugs (eg, RITUXAN [rituximab], HERCEPTIN [trastuzumab], and DARZALEX [daratumumab]). To understand the potential effects of inadvertent intravenous injection of rHuPH20, we investigated the safety profile, pharmacokinetics (PK), and pharmacodynamics (PD) of rHuPH20 administered intravenously. OBJECTIVES: This Phase I, open-label, single-center study in healthy volunteers was designed to assess the safety profile, tolerability, PK, and PD of rHuPH20 administered intravenously. METHODS: Healthy volunteers received 5 mL intravenous infusion of either 10,000 U (n = 12) or 30,000 U (n = 12) rHuPH20 over 5 minutes. Blood samples for PK and PD analysis were obtained at baseline and at various times after initiation of infusion. Adverse events and laboratory parameters were measured to assess the safety profile and tolerability of the intravenous infusion. The PK of rHuPH20 was assessed using both an enzymatic assay and a mass-based immunoassay, and plasma hyaluronan concentrations were measured as a PD marker using an HPLC-MS/MS disaccharide assay. RESULTS: All 24 volunteers (mean age = 36.5 years) completed the study, and no serious adverse events were reported in either treatment group. Overall, 2 adverse events (both Grade 1) were reported; catheter site pain in the 10,000 U group and hypotension in the 30,000 U group. Plasma concentrations of rHuPH20 increased during the 5-minute intravenous infusion (median tmax = 6 minutes from intravenous initiation) followed by a rapid plasma clearance (t1/2 ∼10 minutes from intravenous initiation). Plasma hyaluronan concentrations increased with dose and time (tmax range = 45‒120 minutes from intravenous initiation) and returned to baseline within 1 week of administration. Changes in both PK and PD measurements appeared proportional to dose. CONCLUSIONS: The study demonstrated that intravenous administration of up to 30,000 U rHuPH20 was well tolerated, rapidly cleared from the plasma, and did not appear to be associated with any serious adverse effects at doses used in subcutaneous therapeutic products. (Curr Ther Res Clin Exp. 2020; 81).

10.
Popul Health Metr ; 16(1): 16, 2018 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-30458804

RESUMEN

BACKGROUND: Accurate and reliable hospital information on the pattern and causes of death is important to monitor and evaluate the effectiveness of health policies and programs. The objective of this study was to assess the availability, accessibility, and quality of hospital mortality data in Tanzania. METHODS: This cross-sectional study involved selected hospitals of Tanzania and was carried out from July to October 2016. Review of hospital death registers and forms was carried out to cover a period of 10 years (2006-2015). Interviews with hospital staff were conducted to seek information as regards to tools used to record mortality data, staff involved in recording and availability of data storage and archiving facilities. RESULTS: A total of 247,976 death records were reviewed. The death register was the most (92.3%) common source of mortality data. Other sources included the International Classification of Diseases (ICD) report forms, Inpatient registers, and hospital administrative reports. Death registers were available throughout the 10-year period while ICD-10 forms were available for the period of 2013-2015. In the years between 2006 and 2010 and 2011-2015, the use of death register increased from 82 to 94.9%. Three years after the introduction of ICD-10 procedure, the forms were available and used in 28% (11/39) hospitals. The level of acceptable data increased from 69% in 2006 to 97% in 2015. Inconsistency in the language used, use of non-standard nomenclature for causes of death, use of abbreviations, poorly and unreadable handwriting, and missing variables were common data quality challenges. About 6.3% (n = 15,719) of the records had no patient age, 3.5% (n = 8790) had no cause of death and ~ 1% had no sex indicated. The frequency of missing sex variable was most common among under-5 children. Data storage and archiving in most hospitals was generally poor. Registers and forms were stored in several different locations, making accessibility difficult. CONCLUSION: Overall, this study demonstrates gaps in hospital mortality data availability, accessibility, and quality, and highlights the need for capacity strengthening in data management and periodic record reviews. Policy guidelines on the data management including archiving are necessary to improve data.


Asunto(s)
Mortalidad Hospitalaria , Registros de Hospitales/normas , Registros Médicos/normas , Estudios Transversales , Exactitud de los Datos , Certificado de Defunción , Humanos , Tanzanía/epidemiología
11.
Ann Emerg Med ; 71(6): 737-742, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29107408

RESUMEN

STUDY OBJECTIVE: Patients with end-stage renal disease commonly visit the emergency department (ED). The purpose of this investigation is to examine the prevalence of baseline abnormal lactate levels and to evaluate the effects of hemodialysis on serum lactate levels. METHODS: This was a prospective observational cohort study performed at an outpatient dialysis facility at an urban tertiary care hospital. The study consisted of 226 patients with end-stage renal disease who were receiving long-term hemodialysis and were enrolled during a 2-day period at the beginning of December 2015. Blood drawn for lactate levels was immediately analyzed before and after hemodialysis sessions. All patients completed their hemodialysis sessions. RESULTS: The prevalence of an abnormal lactate level (greater than 1.8 mmol/L) before hemodialysis was 17.7% (n=40). Overall, lactate levels decreased by 27% (SD 35%) after hemodialysis, with a decrease of 37% (SD 31%) for subgroups with a lactate level of 1.9 to 2.4 mmol/L, and 62% (SD 14%) with a lactate of 2.5 to 3.9 mmol/L. CONCLUSION: The data presented help providers understand the prevalence of abnormal lactate values in an outpatient end-stage renal disease population. After hemodialysis, lactate levels decreased significantly. This information may help medical providers interpret lactate values when patients with end-stage renal disease present to the ED.


Asunto(s)
Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Ácido Láctico/sangre , Diálisis Renal , Biomarcadores/sangre , Servicio de Urgencia en Hospital , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sepsis/diagnóstico
12.
Opt Express ; 25(10): 11103-11123, 2017 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-28788793

RESUMEN

A SPAD-based line sensor fabricated in 130 nm CMOS technology capable of acquiring time-resolved fluorescence spectra (TRFS) in 8.3 milliseconds is presented. To the best of our knowledge, this is the fastest time correlated single photon counting (TCSPC) TRFS acquisition reported to date. The line sensor is an upgrade to our prior work and incorporates: i) parallelized interface from sensor to surrounding circuitry enabling high line rate to the PC (19,000 lines/s) and ii) novel time-gating architecture where detected photons in the OFF region are rejected digitally after the output stage of the SPAD. The time-gating architecture was chosen to avoid electrical transients on the SPAD high voltage supplies when gating is achieved by excess bias modulation. The time-gate has an adjustable location and time window width allowing the user to focus on time-events of interest. On-chip integrated center-of-mass (CMM) calculations provide efficient acquisition of photon arrivals and direct lifetime estimation of fluorescence decays. Furthermore, any of the SPC, TCSPC and on-chip CMM modes can be used in conjunction with the time-gating. The higher readout rate and versatile architecture greatly empower the user and will allow widespread applications across many techniques and disciplines. Here we focused on 3 examples of TRFS and time-gated Raman spectroscopy: i) kinetics of chlorophyll A fluorescence from an intact leaf; ii) kinetics of a thrombin biosensor FRET probe from quenched to fluorescence states; iii) ex vivo mouse lung tissue autofluorescence TRFS; iv) time-gated Raman spectroscopy of toluene at 3056 cm-1 peak. To the best of our knowledge, we detect spectrally for the first time the fast rise in fluorescence lifetime of chlorophyll A in a measurement over single fluorescent transient.


Asunto(s)
Óptica y Fotónica , Espectrometría Raman/métodos , Animales , Clorofila/análisis , Clorofila A , Fluorescencia , Pulmón/química , Ratones
14.
Curr Opin Crit Care ; 22(5): 416-23, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27583584

RESUMEN

PURPOSE OF REVIEW: Protocolized care for early shock resuscitation (PCESR) has been intensely examined over the last decade. The purpose is to review the pathophysiologic basis, historical origin, clinical applications, components and outcome implications of PCESR. RECENT FINDINGS: PCESR is a multifaceted systems-based approach that includes early detection of high-risk patients and interventions to rapidly reverse hemodynamic perturbations that result in global or regional tissue hypoxia. It has been applied to perioperative surgery, trauma, cardiology (heart failure and acute myocardial infarction), pulmonary embolus, cardiac arrest, undifferentiated shock, postoperative cardiac surgery and pediatric septic shock. When this approach is used for adult septic shock, in particular, it is associated with a mortality reduction from 46.5 to less than 30% over the last 2 decades. Challenges to these findings are seen when repeated trials contain enrollment, diagnostic and therapeutic methodological differences. SUMMARY: PCESR is more than a hemodynamic optimization procedure. It also provides an educational framework for the less experienced and objective recognition of clinical improvement or deterioration. It further minimizes practices' variation and provides objective measures that can be audited, evaluated and amendable to continuous quality improvement. As a result, morbidity and mortality are improved.


Asunto(s)
Resucitación/métodos , Choque Séptico/terapia , Diagnóstico Precoz , Humanos , Mejoramiento de la Calidad , Sepsis/fisiopatología , Choque Séptico/fisiopatología , Resultado del Tratamiento
15.
Biomarkers ; 21(2): 180-5, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26754286

RESUMEN

OBJECTIVE: To compare plasma levels of F-actin, G-actin and thymosin beta 4 (TB4) in humans with septic shock, noninfectious systemic inflammatory response syndrome (SIRS) and healthy controls. RESULTS: F-actin was significantly elevated in septic shock as compared with noninfectious SIRS and healthy controls. G-actin levels were greatest in the noninfectious SIRS group but significantly elevated in septic shock as compared with healthy controls. TB4 was not detectable in the septic shock or noninfectious SIRS group above the assay's lowest detection range (78 ng/ml). CONCLUSIONS: F-actin is significantly elevated in patients with septic shock as compared with noninfectious SIRS. F-actin and the F:G-actin ratio are potential biomarkers for the diagnosis of septic shock.


Asunto(s)
Actinas/sangre , Biomarcadores/sangre , Choque Séptico/sangre , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Adulto , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Choque Séptico/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Timosina/sangre
16.
Crit Care ; 20(1): 160, 2016 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-27364620

RESUMEN

Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions.


Asunto(s)
Planificación de Atención al Paciente , Sepsis/terapia , Choque Séptico/terapia , Hemodinámica/fisiología , Humanos , Resucitación/métodos , Sepsis/mortalidad , Sepsis/fisiopatología , Choque Séptico/mortalidad , Choque Séptico/fisiopatología
17.
J Emerg Med ; 50(6): 809-17, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27210904

RESUMEN

BACKGROUND: Optimization of tissue oxygen delivery to meet consumption demands is important in the resuscitation of critically ill patients. Central venous oxygen saturation (ScvO2) and lactate levels are often used to guide resuscitation; however, invasive monitoring is required for the former. Clinicians searching for less invasive alternatives may consider using peripheral venous oxygen saturation (SpvO2) and lactate levels as a substitute. OBJECTIVES: To determine the relationship between SpvO2 and ScvO2 and peripheral and central lactate levels. METHODS: All patients with a central venous catheter in an academic emergency department and intensive care unit were eligible for the study. Blood was obtained simultaneously from a central and peripheral vein and measured for oxygen saturation and lactate levels. Results were analyzed using intraclass correlation coefficient (ICC), Bland-Altman plots, and receiver operating characteristic curves. RESULTS: Seventy-nine paired blood samples were analyzed. SpvO2 and ScvO2 have moderate agreement: ICC = 0.53 (95% confidence interval [CI] 0.35-0.67). A Bland-Altman plot revealed substantial bias (-4.47; limits of agreement -38.6, 29.6). SpvO2 ≥ 85% was 90% specific for ScvO2 ≥ 70%, and SpvO2 of ≤ 55% had a 94% sensitivity for ScvO2 < 70%. Central and peripheral venous lactate levels showed almost perfect agreement: ICC = 0.92 (95% CI 0.87-0.95), bias of 0.46 (limits of agreement -1.78-2.70). CONCLUSION: SpvO2 and ScvO2 have moderate agreement. There was excellent agreement between peripheral and central lactate levels, making them interchangeable. The clinical implications of these substitutions in real-time patient management require further study.


Asunto(s)
Ácido Láctico/análisis , Oximetría/métodos , Oxígeno/análisis , Anciano , Anciano de 80 o más Años , Análisis de los Gases de la Sangre/métodos , Catéteres Venosos Centrales , Femenino , Humanos , Ácido Láctico/sangre , Masculino , Persona de Mediana Edad , Oximetría/normas , Oxígeno/sangre , Estudios Prospectivos , Choque/diagnóstico , Choque/terapia
18.
Foot Ankle Surg ; 22(4): 248-253, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27810023

RESUMEN

INTRODUCTION: Currently there is no consensus regarding the use of bilateral simultaneous percutaneous surgery for Hallux valgus treatment. Although the technique described in M. Prado's book, recommends operating only one foot at a time there are no published studies confirming it. The aim of this study was to evaluate whether there is a difference between the results of patients that have been percutaneously operated on one foot and those operated on both feet at the same surgical time for mild to moderate Hallux valgus correction. MATERIAL/METHODS: We did a retrospective single centre evaluation of 93 feet (61 patients) with Hallux valgus operated percutaneously. 29 patients were operated unilaterally (group I) and 32 bilaterally simultaneously (group II) between 2005 and 2009. The Metatarsophalangeal angle (MPA), Intermetatarsal angle (IMA) and Distal metatarsal articular angle (DMAA) were evaluated pre- and postoperatively. The AOFAS score, the degree of patients' satisfaction and the complications were evaluated postoperatively. RESULTS: The mean follow-up was 24.0 months in group I, and 28.0 in group II. The average postoperative AOFAS score was 86.8, 82.9 in group I and 88.6 in group II (p>0.05). 90.6% were satisfied or very satisfied in group I, and 89.7% in group II (p>0.05). There was no statistically significant difference (p>0.05) in the average correction of MPA, DMAA, and IMA. The complications rate was similar in both groups. CONCLUSIONS: The similar results obtained in both groups suggest that the simultaneous bilateral percutaneous surgery gives equivalent results to the unilateral, which has an important socioeconomic impact since there is only one recovery time for both feet. Further research is needed.


Asunto(s)
Hallux Valgus/diagnóstico por imagen , Hallux Valgus/cirugía , Osteotomía/métodos , Dolor Postoperatorio/fisiopatología , Satisfacción del Paciente/estadística & datos numéricos , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Tempo Operativo , Radiografía/métodos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
19.
Kidney Int ; 88(4): 804-14, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25993322

RESUMEN

A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this, we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular-weight proteins and acute-phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and N-acetylaspartate were inversely correlated with the majority of significantly downregulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes were not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness.


Asunto(s)
Lesión Renal Aguda/sangre , Proteínas Sanguíneas/metabolismo , Riñón/metabolismo , ARN Mensajero/sangre , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Biología de Sistemas , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/genética , Lesión Renal Aguda/fisiopatología , Lesión Renal Aguda/terapia , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Enfermedad Crítica , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Riñón/fisiopatología , Pruebas de Función Renal , Masculino , Metabolómica , Persona de Mediana Edad , Proteómica , Diálisis Renal , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/genética , Síndrome de Respuesta Inflamatoria Sistémica/terapia , Integración de Sistemas , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos
20.
Opt Express ; 23(26): 33634-40, 2015 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-26832027

RESUMEN

We demonstrate a short-wavelength hybrid-cavity vertical-cavity surface-emitting laser (VCSEL) heterogeneously integrated on silicon. A GaAs-based "half-VCSEL" has been attached to a dielectric distributed Bragg reflector (DBR) on a silicon wafer using ultra-thin divinylsiloxane-bis-benzocyclobutene (DVS-BCB) adhesive bonding, thereby creating a cavity with the standing-wave optical field extending over the silicon- and GaAs-based parts of the cavity. A 9 µm oxide aperture diameter VCSEL with a threshold current of 1.2 mA produces 1.6 mW optical output power at 6.0 mA bias current with a wavelength of ~845 nm.

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