RESUMEN

This pilot study was designed to investigate the effects of a holistic lighting intervention on the quality of life for individuals with low vision. Sixty participants (44 women; median age 69 years) with visual impairment received lighting interventions, including a home visit and consultation in a lighting lab. Assisted by low vision consultants, participants evaluated their performance using the Canadian Occupational Performance Measure (COPM) before and after the intervention. Improvements in visual functioning and quality of life were evaluated using the 39-item National Eye Institute Visual Function Questionnaire (NEI VFQ-39), the Groffman Visual Tracing Test, and the Farnsworth Dichotomous Test (D15). Following the lighting intervention, scores improved for all activities in the COPM (p < 0.01), for near activities and vision-specific role difficulties in the VFQ-39 (p < 0.05), and overall in the D15 test (p < 0.05). These results suggest the intervention provided an effective method for improving the participants' quality of life and performance.

Asunto(s)

Terapia Ocupacional , Baja Visión , Humanos , Femenino , Anciano , Calidad de Vida , Iluminación , Proyectos Piloto , Agudeza Visual , Canadá , Trastornos de la Visión , Encuestas y Cuestionarios , Perfil de Impacto de Enfermedad

RESUMEN

STUDY QUESTION: Do paracetamol (N-acetyl-para-aminophenol (APAP) or acetaminophen) and/or its metabolites affect human sperm Ca2+-signalling and function? SUMMARY ANSWER: While APAP itself does not interact with Ca2+-signalling in human sperm, its metabolite N-arachidonoyl phenolamine (AM404), produced via fatty acid amide hydrolase (FAAH), interferes with human sperm Ca2+-signalling and function through a suggested CatSper channel-dependent action. WHAT IS KNOWN ALREADY: Studies have shown that adult men with high urinary levels of over-the-counter mild analgesic APAP have impaired sperm motility and increased time-to-pregnancy. STUDY DESIGN, SIZE, DURATION: This study consists of (i) an in vivo human pharmaceutical APAP exposure experiment to understand to what degree APAP reaches the sperm cells in the seminal fluid; (ii) in vitro calcium imaging and functional experiments in freshly donated human sperm cells to investigate CatSper channel-dependent activation by APAP and its metabolites; and (iii) experiments to understand the in situ capabilities of human sperm cells to form APAP metabolite AM404. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three healthy young males participated in the in vivo human exposure experiment after prior consent. Human semen samples were provided by healthy young volunteer donors after prior consent on the day of the in vitro experiments. MAIN RESULTS AND THE ROLE OF CHANCE: Pharmaceutical APAP exposure reaches the seminal plasma in high micromolar concentrations and accumulates in the seminal plasma between 3 and 5 days of exposure (P-value 0.023). APAP and its primary metabolite 4-aminophenol (4AP) do not interact with human sperm Ca2+-signalling. Instead, the APAP metabolite AM404 produced via FAAH interferes with human sperm Ca2+-signalling through a CatSper-dependent action. Also, AM404 significantly increases sperm cell penetration into viscous mucous (P-value of 0.003). FAAH is functionally expressed in human sperm cells in the neck/midpiece region, as evidenced by immunohistochemical staining and the ability of human sperm cells to hydrolyse the fluorogenic FAAH substrate arachidonyl 7-amino, 4-methyl coumarin amide in an FAAH-dependent manner. Importantly, human sperm cells have the capacity to form AM404 in situ after exposure to 4AP (P-value 0.0402 compared to vehicle-treated sperm cells). LIMITATIONS, REASONS FOR CAUTION: The experiments were conducted largely in vitro. Future studies are needed to test whether APAP can disrupt human sperm function in vivo through the action of AM404. WIDER IMPLICATIONS OF THE FINDINGS: We hypothesize that these observations could, at least in part, be responsible for the negative association between male urinary APAP concentrations, sperm motility and time-to-pregnancy. STUDY FUNDING/COMPETING INTEREST(S): D.M.K. is funded by the Lundbeck Foundation, grant number R324-2019-1881, and the Svend Andersen Foundation. A.R. is funded by a BRIDGE-Translational Excellence Programme grant funded by the Novo Nordisk Foundation, grant agreement number: NNF18SA0034956. All authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Asunto(s)

Acetaminofén , Motilidad Espermática , Acetaminofén/farmacología , Adulto , Ácidos Araquidónicos , Calcio/metabolismo , Canales de Calcio/metabolismo , Humanos , Masculino , Preparaciones Farmacéuticas/metabolismo , Progesterona/metabolismo , Espermatozoides/metabolismo

RESUMEN

BACKGROUND: People with severe mental illness (SMI) have an increased risk of premature mortality, predominantly due to somatic health conditions. Evidence indicates that primary and tertiary prevention and improved treatment of somatic conditions in patients with SMI could reduce this excess mortality. This paper reports a protocol designed to evaluate the feasibility of a coordinated co-produced care program (SOFIA model, a Danish acronym for Severe Mental Illness and Physical Health in General Practice) in the general practice setting to reduce mortality and improve quality of life in patients with severe mental illness. METHODS: The SOFIA pilot trial is designed as a cluster randomized controlled trial targeting general practices in two regions in Denmark. We aim to include 12 practices, each of which is instructed to recruit up to 15 community-dwelling patients aged 18 and older with SMI. Practices will be randomized by a computer in a ratio of 2:1 to deliver a coordinated care program or usual care during a 6-month study period. A randomized algorithm is used to perform randomization. The coordinated care program includes educational training of general practitioners and their clinical staff educational training of general practitioners and their clinical staff, which covers clinical and diagnostic management and focus on patient-centered care of this patient group, after which general practitioners will provide a prolonged consultation focusing on individual needs and preferences of the patient with SMI and a follow-up plan if indicated. The outcomes will be parameters of the feasibility of the intervention and trial methods and will be assessed quantitatively and qualitatively. Assessments of the outcome parameters will be administered at baseline, throughout, and at end of the study period. DISCUSSION: If necessary the intervention will be revised based on results from this study. If delivery of the intervention, either in its current form or after revision, is considered feasible, a future, definitive trial to determine the effectiveness of the intervention in reducing mortality and improving quality of life in patients with SMI can take place. Successful implementation of the intervention would imply preliminary promise for addressing health inequities in patients with SMI. TRIAL REGISTRATION: The trial was registered in Clinical Trials as of November 5, 2020, with registration number NCT04618250 . Protocol version: January 22, 2021; original version.

RESUMEN

Mesoscale convective systems (MCSs) are complexes of thunderstorms that become organized and cover hundreds of kilometres over several hours. MCSs are prolific rain producers in the tropics and mid-latitudes and are the major cause of warm-season flooding. Traditionally, climate models have difficulties in simulating MCSs partly due to the misrepresentation of complex process interactions that operate across a large range of scales. Significant improvements in simulating MCSs have been found in kilometre-scale models that explicitly simulate deep convection. However, these models operate in the grey zone of turbulent motion and have known deficiencies in simulating small-scale processes (e.g. entrainment, vertical mass transport). Here, we perform mid-latitude idealized ensemble MCS simulations under current and future climate conditions in three atmospheric regimes: hydrostatic (12 km horizontal grid spacing; Δx), non-hydrostatic (Δx = 4, 2 and 1 km) and large eddy scale (Δx = 500 m and 250 m). Our results show a dramatic improvement in simulating MCS precipitation, movement, cold pools, and cloud properties when transitioning from 12 km to 4 km Δx. Decreasing Δx beyond 4 km results in modest improvements except for up- and downdraft sizes, average vertical mass fluxes, and cloud top height and temperature, which continue to change. Most important for climate modelling is that Δx = 4 km simulations reliably capture most MCS climate change signals compared to those of the Δx = 250 m runs. Significantly different climate change signals are found in Δx = 12 km runs that overestimate extreme precipitation changes by up to 100%. This article is part of a discussion meeting issue 'Intensification of short-duration rainfall extremes and implications for flash flood risks'.

RESUMEN

BACKGROUND: Knowledge about prevalent and deadly combinations of multimorbidity is needed. OBJECTIVE: To determine the nationwide prevalence of multimorbidity and estimate mortality for the most prevalent combinations of one to five diagnosis groups. Furthermore, to assess the excess mortality of the combination of two groups compared to the product of mortality associated with the single groups. DESIGN: A prospective cohort study using Danish registries and including 3.986.209 people aged ≥18 years on 1 January, 2000. Multimorbidity was defined as having diagnoses from at least 2 of 10 diagnosis groups: lung, musculoskeletal, endocrine, mental, cancer, neurological, gastrointestinal, cardiovascular, kidney, and sensory organs. Logistic regression (odds ratios, ORs) and ratio of ORs (ROR) were used to study mortality and excess mortality. RESULTS: Prevalence of multimorbidity was 7.1% in the Danish population. The most prevalent combination was the musculoskeletal-cardiovascular (0.4%), which had double the mortality (OR, 2.03) compared to persons not belonging to any of the diagnosis groups but showed no excess mortality (ROR, 0.97). The neurological-cancer combination had the highest mortality (OR, 6.35), was less prevalent (0.07%), and had no excess mortality (ROR, 0.94). Cardiovascular-lung was moderately prevalent (0.2%), had high mortality (OR, 5.75), and had excess mortality (ROR, 1.18). Endocrine-kidney had high excess mortality (ROR, 1.81) and cancer-mental had low excess mortality (ROR, 0.66). Mortality increased with the number of groups. CONCLUSIONS: All combinations had increased mortality risk with some of them having up to a six-fold increased risk. Mortality increased with the number of diagnosis groups. Most combinations did not increase mortality above that expected, that is, were additive rather than synergistic.

RESUMEN

Maximally tolerated dose (MTD) and metronomic dose chemotherapeutic approaches alter the immune system and the angiogenic process in different yet potentially complementary ways. A combination of MTD doxorubicin (MTD-DOX) and metronomic cyclophosphamide (mCTX) protocol was evaluated for safety and effect on circulating regulatory T (Treg) cells. We found that mCTX can be safely administered with MTD-DOX in tumour-bearing dogs. Both combination DOX/mCTX and single-agent DOX resulted in significant depletions of circulating lymphocytes throughout the chemotherapy cycle without apparent selectivity for Tregs. The indiscriminant lymphocyte depletions were similar between dogs randomized to receive DOX and dogs randomized to receive DOX/mCTX, suggesting this effect is because of DOX alone. These findings may have implications as to the therapeutic benefit (or lack thereof) of concurrent combination MTD and metronomic protocols. Future investigations are required to determine the effects and indeed the efficacy of concurrent versus sequential applications of MTD and metronomic chemotherapy protocols.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Doxorrubicina/uso terapéutico , Neoplasias/veterinaria , Linfocitos T Reguladores/efectos de los fármacos , Administración Metronómica/veterinaria , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Enfermedades de los Perros/inmunología , Perros , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Recuento de Linfocitos/veterinaria , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología

RESUMEN

A collaborative trial was conducted to determine the performance characteristics of an analytical method for the quantification of inorganic arsenic (iAs) in food. The method is based on (i) solubilisation of the protein matrix with concentrated hydrochloric acid to denature proteins and allow the release of all arsenic species into solution, and (ii) subsequent extraction of the inorganic arsenic present in the acid medium using chloroform followed by back-extraction to acidic medium. The final detection and quantification is done by flow injection hydride generation atomic absorption spectrometry (FI-HG-AAS). The seven test items used in this exercise were reference materials covering a broad range of matrices: mussels, cabbage, seaweed (hijiki), fish protein, rice, wheat, mushrooms, with concentrations ranging from 0.074 to 7.55mgkg(-1). The relative standard deviation for repeatability (RSDr) ranged from 4.1 to 10.3%, while the relative standard deviation for reproducibility (RSDR) ranged from 6.1 to 22.8%.

Asunto(s)

Arsénico/análisis , Contaminación de Alimentos/análisis , Espectrofotometría Atómica , Agaricales/química , Animales , Bivalvos/química , Brassica/química , Proteínas de Peces/química , Análisis de los Alimentos , Oryza/química , Reproducibilidad de los Resultados , Algas Marinas/química , Triticum/química

RESUMEN

A dynamical downscaling method for probabilistic regional-scale climate change projections was developed to cover the inherent uncertainty associated with multiple general circulation model (GCM) climate simulations. The climatological increments estimated by GCM results were statistically analyzed using the singular vector decomposition. Both positive and negative perturbations from the ensemble mean with the magnitudes of their standard deviations were extracted and added to the ensemble mean of the climatological increments. The analyzed multiple modal increments were utilized to create multiple modal lateral boundary conditions for the future climate regional climate model (RCM) simulations by adding them to reanalysis data. The incremental handling of GCM simulations realized approximated probabilistic climate change projections with the smaller number of RCM simulations. For the probabilistic analysis, three values of a climatological variable simulated by RCMs for a mode were analyzed under an assumption of linear response to the multiple modal perturbations.

RESUMEN

Glioblastoma-initiating cells (GICs) are self-renewing tumorigenic sub-populations, contributing to therapeutic resistance via decreased sensitivity to ionizing radiation (IR). GIC survival following IR is attributed to an augmented response to genotoxic stress. We now report that GICs are primed to handle additional stress due to basal activation of single-strand break repair (SSBR), the main DNA damage response pathway activated by reactive oxygen species (ROS), compared with non-GICs. ROS levels were higher in GICs and likely contributed to the oxidative base damage and single-strand DNA breaks found elevated in GICs. To tolerate constitutive DNA damage, GICs exhibited a reliance on the key SSBR mediator, poly-ADP-ribose polymerase (PARP), with decreased viability seen upon small molecule inhibition to PARP. PARP inhibition (PARPi) sensitized GICs to radiation and inhibited growth, self-renewal, and DNA damage repair. In vivo treatment with PARPi and radiotherapy attenuated radiation-induced enrichment of GICs and inhibited the central cancer stem cell phenotype of tumor initiation. These results indicate that elevated PARP activation within GICs permits exploitation of this dependence, potently augmenting therapeutic efficacy of IR against GICs. In addition, our results support further development of clinical trials with PARPi and radiation in glioblastoma.

Asunto(s)

Glioblastoma/metabolismo , Glioblastoma/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Poli(ADP-Ribosa) Polimerasas/metabolismo , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Daño del ADN , Reparación del ADN , Relación Dosis-Respuesta a Droga , Glioblastoma/terapia , Humanos , Masculino , Ratones , Ratones Desnudos , Células Madre Neoplásicas/efectos de los fármacos , Fenotipo , Ftalazinas/farmacología , Piperazinas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad

RESUMEN

Two of the core tasks of the European Union Reference Laboratory for Heavy Metals in Feed and Food (EU-RL-HM) are to provide advice to the Directorate General for Health and Consumers (DG SANCO) on scientific matters and to organise proficiency tests among appointed National Reference Laboratories. This article presents the results of the 12th proficiency test organised by the EU-RL-HM (IMEP-112) that focused on the determination of total and inorganic arsenic in wheat, vegetable food and algae. The test items used in this exercise were: wheat sampled in a field with a high concentration of arsenic in the soil, spinach (SRM 1570a from NIST) and an algae candidate reference material. Participation in this exercise was open to laboratories from all around the world to be able to judge the state of the art of the determination of total and, more in particular, inorganic arsenic in several food commodities. Seventy-four laboratories from 31 countries registered to the exercise; 30 of them were European National Reference Laboratories. The assigned values for IMEP-112 were provided by a group of seven laboratories expert in the field of arsenic speciation analysis in food. Laboratory results were rated with z and ζ scores (zeta scores) in accordance with ISO 13528. Around 85 % of the participants performed satisfactorily for inorganic arsenic in vegetable food and 60 % did for inorganic arsenic in wheat, but only 20 % of the laboratories taking part in the exercise were able to report satisfactory results in the algae test material.

Asunto(s)

Arsénico/química , Contaminación de Alimentos/legislación & jurisprudencia , Unión Europea , Humanos

RESUMEN

The recent developments on the use of e-pedigree to identify the chain of custody of drugs suggests the use of advanced track and trace technologies such as two-dimensional barcodes and radio frequency identification (RFID) tags. RFID technology is used mainly for valuable commodities such as pharmaceutical products while incorporating additional functionalities like monitoring environmental variables to ensure product safety and quality. In its guidance for the use of RFID technologies for drugs (Compliance Policy Guide Section 400.210), the Food and Drug Administration outlined multiple parameters that would apply to any study or application using RFID. However, drugs approved under a Biologics License Application or protein drugs covered by a New Drug Application were excluded mainly due to concerns about the effects of radio frequency radiation (thermal and/or non-thermal) on biologics. Even though the thermal effects of radio frequency on biologics are relatively well understood, there are few studies in the literature about the non-thermal effects of radio frequency with regards to the protein structure integrity. In this paper, we analyze the non-thermal effects of radio frequency radiation by exposing a wide variety of biologics including biopharmaceuticals with vaccines, hormones, and immunoglobulins, as well as cellular blood products such as red blood cells and whole blood-derived platelets as well as fresh frozen plasma. In order to represent the majority of the frequency spectrum used in RFID applications, five different frequencies (13.56 MHz, 433 MHz, 868 MHz, 915 MHz, and 2.4 GHz) are used to account for the most commonly used international frequency bands for RFID. With the help of specialized radio frequency signal-generating hardware, magnetic and electromagnetic fields are created around the exposed products with power levels greater than Federal Communications Commission-regulated limits. The in vitro test results on more than 100 biopharmaceutical products from eight major pharmaceutical companies as well, as different blood products, show no non-thermal effect by radio frequency radiation. LAY ABSTRACT: Forthcoming requirements, such as the California Board of Pharmacy Track and Trace initiative regarding the use of e-pedigree to identify the chain of custody of drugs, suggest the use of advanced track and trace technologies such as two-dimensional barcodes and radio frequency identification (RFID) tags. When used for pharmaceuticals, RFID technology can support additional functionalities like monitoring temperature to ensure product safety. In its guidance for the use of RFID technologies for drugs, the Food and Drug Administration outlined multiple parameters that would apply to pilot studies using RFID while excluding drugs approved under a Biologics License Application or protein drugs covered by a New Drug Application due to concerns about the effects of radio frequency radiation on biologics. Even though the effects of radio frequency on biologics due to temperature changes are relatively well understood, there are few studies in the literature about other effects of radio frequency that can occur without a noticeable change in temperature. In this paper, we expose a wide variety of biologics including biopharmaceuticals to radio frequency radiation at different frequencies, as well as cellular blood products and plasma to high frequency radiation. The in vitro test results show no detectable effect due to radio frequency radiation.

Asunto(s)

Productos Biológicos , Dispositivo de Identificación por Radiofrecuencia , Seguridad de Productos para el Consumidor , Campos Electromagnéticos , Eritrocitos/efectos de la radiación , Técnicas In Vitro , Preparaciones Farmacéuticas , Ondas de Radio

RESUMEN

The increasing number of resistant bacterial strains in infective endocarditis (IE) emphasizes the need for a constant development of antimicrobials. Linezolid is an oxazolidinone with an effect on Gram-positive cocci. Only a few casuistic reports describe its utilization in the treatment of IE. The objective of this study is to report our experience with linezolid from a large consecutive cohort of IE patients. In a retrospective cohort study, data on 550 consecutive IE patients were collected at two tertiary University Hospitals in Copenhagen, Denmark. The main endpoints were differences in the in-hospital and 12 months post-discharge mortality between IE patients receiving linezolid for a part of the treatment and IE patients receiving conventional treatment. Of the 550 patients enrolled in the study, 38 patients received linezolid treatment and 512 received conventional treatment. Reasons for adding linezolid were antibiotic intolerance (n = 13), nephrotoxicity (n = 5), pharmaceutical interactions (n = 1), inadequate clinical response (n = 14), or inadequate microbial response (n = 5). No significant differences in the cure rate (74 % vs. 71 %, p > 0.05), in-hospital mortality (13 % vs. 14 %, p > 0.05), or post-discharge mortality at 12 months follow-up (26 % vs. 26 %, p > 0.05) were observed. In the current study, we found that linezolid, in general, was well tolerated and associated with the same outcome as in patients with Gram-positive IE treated with other antibiotics.

Asunto(s)

Acetamidas/uso terapéutico , Antibacterianos/uso terapéutico , Endocarditis Bacteriana/tratamiento farmacológico , Enterococcus/patogenicidad , Oxazolidinonas/uso terapéutico , Streptococcus/patogenicidad , Acetamidas/farmacología , Anciano , Antibacterianos/farmacología , Dinamarca/epidemiología , Tolerancia a Medicamentos , Endocarditis Bacteriana/epidemiología , Endocarditis Bacteriana/microbiología , Enterococcus/efectos de los fármacos , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Linezolid , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Oxazolidinonas/farmacología , Estudios Retrospectivos , Streptococcus/efectos de los fármacos , Análisis de Supervivencia , Centros de Atención Terciaria , Resultado del Tratamiento

RESUMEN

Anticoagulant therapy has been anticipated to increase the risk of cerebrovascular complications (CVC) in native valve endocarditis (NVE). This study investigates the relationship between ongoing oral anticoagulant therapy and the incidence of symptomatic CVC in left-sided NVE. In a prospective cohort study, the CVC incidence was compared between NVE patients with and without ongoing warfarin. Among 587 NVE episodes, 48 (8%) occurred in patients on warfarin. A symptomatic CVC was seen in 144 (25%) patients, with only three on warfarin. CVC were significantly less frequent in patients on warfarin (6% vs. 26%, odds ratio [OR] 0.20, 95% confidence interval [CI] 0.06-0.6, p = 0.006). No increase in haemorrhagic lesions was detected in patients on warfarin. Staphylococcus aureus aetiology (adjusted OR [aOR] 6.3, 95% CI 3.8-10.4) and vegetation length (aOR 1.04, 96% CI 1.01-1.07) were risk factors for CVC, while warfarin on admission (aOR 0.26, 95% CI 0.07-0.94), history of congestive heart failure (adjusted OR 0.22, 95% CI 0.1-0.52) and previous endocarditis (aOR 0.1, 95% CI 0.01-0.79) correlated with lower CVC frequency.

Asunto(s)

Anticoagulantes/efectos adversos , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/tratamiento farmacológico , Meningoencefalitis/epidemiología , Meningoencefalitis/microbiología , Warfarina/efectos adversos , Administración Oral , Anciano , Anticoagulantes/administración & dosificación , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Staphylococcus aureus/aislamiento & purificación , Warfarina/administración & dosificación

RESUMEN

Penicillium roqueforti, Penicillium paneum, Monascus ruber, Alternaria tenuissima, Fusarium graminearum, Fusarium avenaceum, Byssochlamys nivea and Aspergillus fumigatus have previously been identified as major fungal contaminants of Danish maize silage. In the present study their metabolite production and in vitro cytotoxicity have been determined for fungal agar and silage extracts. All 8 fungal species significantly affected Caco-2 cell viability in the resazurin assay, with large variations for each species and growth medium. The 50% inhibition concentrations (IC(50)) of the major P. roqueforti metabolites roquefortine C (48 µg/mL), andrastin A (>50 µg/mL), mycophenolic acid (>100 µg/mL) and 1-hydroxyeremophil-7(11),9(10)-dien-8-one (>280 µg/mL) were high. Fractionating of agar extracts identified PR-toxin as an important cytotoxic P. roqueforti metabolite, also detectable in maize silage. The strongly cytotoxic B. nivea and P. paneum agar extracts contained patulin above the IC(50) of 0.6 µg/mL, however inoculated onto maize silage B. nivea and P. paneum did not produce patulin (>371 µg/kg). Still B. nivea infected maize silage containing mycophenolic acid (∼50 mg/kg), byssochlamic acid and other metabolites, was cytotoxic. In contrast hot-spots of P. roqueforti, P. paneum, M. ruber and A. fumigatus were not more cytotoxic than uninoculated silage.

Asunto(s)

Hongos/patogenicidad , Zea mays/microbiología , Células CACO-2 , Humanos , Concentración 50 Inhibidora

RESUMEN

This paper describes a method for determination of 27 mycotoxins and other secondary metabolites in maize silage. The method focuses on analytes which are known to be produced by common maize and maize-silage contaminants. A simple pH-buffered sample extraction was developed on the basis of a very fast and simple method for analysis of multiple pesticide residues in food known as QuEChERS. The buffering effectively ensured a stable pH in samples of both well-ensiled maize (pH < 4) and of hot spots with fungal infection (pH > 7). No further clean-up was performed before analysis using liquid chromatography-tandem mass spectrometry. The method was successfully validated for determination of eight analytes qualitatively and 19 quantitatively. Matrix-matched calibration standards were used giving recoveries ranging from 37% to 201% with the majority between 60% and 115%. Repeatability (5-27% RSD(r)) and intra-laboratory reproducibility (7-35% RSD(IR)) was determined. The limit of detection (LOD) for the quantitatively validated analytes ranged from 1 to 739 microg kg(-1). Validation results for citrinin, fumonisin B(1) and fumonisin B(2) were unsatisfying. The method was applied to 20 selected silage samples and alternariol monomethyl ether, andrastin A, alternariol, citreoisocoumarin, deoxynivalenol, enniatin B, fumigaclavine A, gliotoxin, marcfortine A and B, mycophenolic acid, nivalenol, roquefortine A and C and zearalenone were detected.

Asunto(s)

Cromatografía Liquida/métodos , Micotoxinas/análisis , Ensilaje/análisis , Espectrometría de Masas en Tándem/métodos , Zea mays/química , Límite de Detección

RESUMEN

The potential of C(60)-nanoparticles (Buckminster fullerenes) as contaminant carriers in aqueous systems was studied in a series of toxicity tests with algae (Pseudokirchneriella subcapitata) and crustaceans (Daphnia magna). Four common environmental contaminants (atrazine, methyl parathion, pentachlorophenol (PCP), and phenanthrene) were used as model compounds, representing different physico-chemical properties and toxic modes of action. The aggregates of nano-C(60) formed over 2 months of stirring in water were mixed with model compounds 5 days prior to testing. Uptake and excretion of phenanthrene in 4-days-old D. magna was studied with and without addition of C(60) in aqueous suspensions. It was found that 85% of the added phenanthrene sorbed to C(60)-aggregates >200 nm whereas about 10% sorption was found for atrazine, methyl parathion, and pentachlorophenol. In algal tests, the presence of C(60)-aggregates increased the toxicity of phenanthrene with 60% and decreased toxicity of PCP about 1.9 times. Addition of C(60)-aggregates reduced the toxicity of PCP with 25% in tests with D. magna, whereas a more than 10 times increase in toxicity was observed for phenanthrene when results were expressed as water phase concentrations. Thus, results from both toxicity tests show that phenanthrene sorbed to C(60)-aggregates is available for the organisms. For atrazine and methyl parathion no statistically significant differences in toxicities could be observed in algal and daphnid tests as a result of the presence of C(60)-aggregates. In bioaccumulation studies with phenanthrene in D. magna it was found that the uptake of phenanthrene was faster when C(60) was present in suspension and that a 1.7 times higher steady-state concentration was reached in the animals. However, a very fast clearance took place when animals were transferred to clean water resulting in no accumulation of phenanthrene. This study is the first to demonstrate the influence of C(60)-aggregates on aquatic toxicity and bioaccumulation of other environmentally relevant contaminants. The data provided underline that not only the inherent toxicity of manufactured nanoparticles, but also interactions with other compounds and characterisation of nanoparticles in aqueous suspension are of importance for risk assessment of nanomaterials.

Asunto(s)

Chlorophyta/efectos de los fármacos , Daphnia/efectos de los fármacos , Fulerenos/toxicidad , Fenantrenos/toxicidad , Contaminantes Químicos del Agua/farmacocinética , Contaminantes Químicos del Agua/toxicidad , Animales , Atrazina/metabolismo , Atrazina/farmacocinética , Atrazina/toxicidad , Disponibilidad Biológica , Chlorophyta/crecimiento & desarrollo , Fulerenos/análisis , Fulerenos/metabolismo , Metil Paratión/metabolismo , Metil Paratión/farmacocinética , Metil Paratión/toxicidad , Pentaclorofenol/metabolismo , Pentaclorofenol/farmacocinética , Pentaclorofenol/toxicidad , Fenantrenos/metabolismo , Fenantrenos/farmacocinética , Suspensiones , Factores de Tiempo , Contaminantes Químicos del Agua/metabolismo

RESUMEN

Human immunodeficiency virus type 1 (HIV-1) clade C causes >50% of all HIV infections worldwide, and an estimated 90% of all transmissions occur mucosally with R5 strains. A pathogenic R5 simian-human immunodeficiency virus (SHIV) encoding HIV clade C env is highly desirable to evaluate candidate AIDS vaccines in nonhuman primates. To this end, we generated SHIV-1157i, a molecular clone from a Zambian infant isolate that carries HIV clade C env. SHIV-1157i was adapted by serial passage in five monkeys, three of which developed peripheral CD4(+) T-cell depletion. After the first inoculated monkey developed AIDS at week 137 postinoculation, transfer of its infected blood to a naïve animal induced memory T-cell depletion and thrombocytopenia within 3 months in the recipient. In parallel, genomic DNA from the blood donor was amplified to generate the late proviral clone SHIV-1157ipd3. To increase the replicative capacity of SHIV-1157ipd3, an extra NF-kappaB binding site was engineered into its 3' long terminal repeat, giving rise to SHIV-1157ipd3N4. This virus was exclusively R5 tropic and replicated more potently in rhesus peripheral blood mononuclear cells than SHIV-1157ipd3 in the presence of tumor necrosis factor alpha. Rhesus macaques of Indian and Chinese origin were next inoculated intrarectally with SHIV-1157ipd3N4; this virus replicated vigorously in both sets of monkeys. We conclude that SHIV-1157ipd3N4 is a highly replication-competent, mucosally transmissible R5 SHIV that represents a valuable tool to test candidate AIDS vaccines targeting HIV-1 clade C Env.

Asunto(s)

Infecciones por VIH/transmisión , VIH-1/clasificación , VIH-1/patogenicidad , Receptores de Citocinas/metabolismo , Síndrome de Inmunodeficiencia Adquirida del Simio/transmisión , Virus de la Inmunodeficiencia de los Simios/patogenicidad , Administración Rectal , Secuencia de Aminoácidos , Animales , Quimera , Clonación Molecular , Productos del Gen env/genética , Infecciones por VIH/virología , VIH-1/genética , Humanos , Lactante , Macaca mulatta , Datos de Secuencia Molecular , Receptores CXCR5 , Receptores de Quimiocina , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/genética , Replicación Viral

RESUMEN

BACKGROUND AND PURPOSE: The purpose of this study was to examine the effects of D-amphetamine (D-amph) and physical therapy separately or combined on fine motor performance, gross motor performance and cognition after middle cerebral artery thromboembolization in rats. METHODS: Seventy-four rats were trained in appropriate cognitive and motor behaviours. Thirteen animals were sham-operated and fifty-nine animals were embolized in the right carotid territory. Animals were randomly assigned to five groups: 1) SHAM (non-embolized, saline), 2) CONTROL (embolized, saline), 3) D-AMPH (embolized, D-amph), 4) THERAPY (embolized, saline + physical therapy) and 5) D-AMPH + THERAPY (embolized, D-amph + physical therapy). Rats of the groups 4-5 underwent d-amph or saline treatment on days 1, 3, 5 and 7 after surgery and were re-trained for 1 h starting 60 min after each treatment. During this time, rats were allowed to voluntarily engage in suitable cognitive or motor behaviours in order to obtain food. Animals from all groups were re-tested during days 21-28 after surgery. RESULTS: No differences in infarct volumes were observed between the groups of embolized animals. When evaluating performances on days 21-28 after surgery, rats of the SHAM and THERAPY groups had better fine motor performance than those of the CONTROL (P < 0.05), whereas rats of SHAM and D-AMPH groups achieved better cognitive performance than CONTROL rats (P < 0.05). No significant differences were observed between any groups regarding gross motor performance. CONCLUSIONS: After embolization, physical therapy improved fine motor performance and D-amph accelerated rehabilitation of cognitive performance as observed in the rats of the THERAPY and D-AMPH groups. As a result of the administration of a high dose of D-amph, the rats of the D-AMPH + THERAPY combination group failed to engage in physical therapy during D-amph intoxication, thereby limiting any promotion of rehabilitation by combining physical therapy and D-amph.

Asunto(s)

Estimulantes del Sistema Nervioso Central/uso terapéutico , Trastornos del Conocimiento/rehabilitación , Dextroanfetamina/uso terapéutico , Embolia Intracraneal/complicaciones , Embolia Intracraneal/rehabilitación , Trastornos de la Destreza Motora/etiología , Trastornos de la Destreza Motora/rehabilitación , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Estimulantes del Sistema Nervioso Central/farmacología , Trastornos del Conocimiento/etiología , Dextroanfetamina/farmacología , Modelos Animales de Enfermedad , Masculino , Arteria Cerebral Media , Modalidades de Fisioterapia , Ratas , Ratas Sprague-Dawley , Tromboembolia

RESUMEN

The concentrations of CF(3)-containing compounds in archived air samples collected at Cape Meares, Oregon, from 1978 to 1997, at Point Barrow, Alaska, from 1995 to 1998, and at Palmer Station, Antarctica, from 1991 to 1997, were determined by high resolution gas chromatography and high resolution mass spectrometry. The CF(3)-containing compounds measured by this method and discussed here are: the perfluorinated compound, C(3)F(8) (FC 218); four perhalogenated compounds, CF(3)Cl (CFC 13), CF(3)CF(2)Cl (CFC 115), CF(3)CFCl(2) (CFC 114a), and CF(3)Br (Halon 1301); and three hydrofluorocompounds, CF(3)H (HFC 23), CF(3)CH(3) (HFC 143a), and CF(3)CH(2)F (HFC 134a). For four of these compounds, very few measurements have been previously reported. The atmospheric concentrations of all of the CF(3)-containing compounds continuously increased in time over the sample collection periods. From these data, the annual rates of emission into the atmosphere have been estimated. The emission rates fall into one of three distinct categories. The annual emission rates of C(3)F(8), CF(3)H, CF(3)CH(3), and CF(3)CH(2)F have continuously increased over the last two decades. That of CF(3)CFCl(2) has decreased continuously. Emission rates for CF(3)Cl, CF(3)CF(2)Cl, and CF(3)Br reached maximum levels in the late 1980s, and have been decreasing in the 1990s. The emission rates of C(3)F(8), CF(3)CH(3) and CF(3)CH(2)F were nearly zero 20 years ago but have increased rapidly during the last decade.

Asunto(s)

Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Hidrocarburos Halogenados/análisis , Modelos Químicos , Alaska , Regiones Antárticas , Cromatografía de Gases y Espectrometría de Masas , Oregon

RESUMEN

This literature review synthesizes available studies on Hmong agricultural practices, patterns of childhood growth and development of Hmong children in the context of injury prevention, and potential application or adaptation of the North American Guidelines for Children's Agricultural Tasks (Lee and Marlenga, 1999) for Hmong children working in the U.S. Data from qualitative interviews, focus groups, case studies, and surveys were collected, categories were determined, and themes were identified. Field tools and practices, gender roles, and reasons for farming were examined, as well as physical and cognitive development of Hmong children and Hmong parenting techniques to describe factors related to farm task assignment of children. Current agricultural practices of Hmong in the U.S. can be described as generally small-scale operations that use mainly hand tools, manual labor, and local direct-marketing techniques. Specific practices include thinning, weeding, and hoeing; carrying tools, buckets, or baskets; setting plant supports; and watering. Hmong children appear to be given greater amounts of responsibility at earlier ages than North American children. Hmong parenting practices, as would be used in task assignment, are somewhat more authoritarian-based and lead to psychosocial skills that are more group-oriented than individual-oriented. Hmong children were found to be shorter than children in the U.S. of the same ages. This review suggests that the NAGCAT cannot be literally translated and disseminated to Hmong farming families as an injury prevention intervention. Further information is needed about what farm tasks Hmong children do and how Hmong parents assign those tasks to children.

Asunto(s)

Accidentes de Trabajo/prevención & control , Agricultura/normas , Asiático/etnología , Empleo/normas , Guías como Asunto , Salud Laboral , Responsabilidad Parental/etnología , Adolescente , Asiático/psicología , Estatura/etnología , Niño , Desarrollo Infantil , Cognición , Femenino , Identidad de Género , Humanos , Laos/etnología , Masculino , Estados Unidos