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1.
Genes Dev ; 34(7-8): 598-618, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-32115407

RESUMEN

Gastrulation in the early postimplantation stage mammalian embryo begins when epiblast cells ingress to form the primitive streak or develop as the embryonic ectoderm. The DNA dioxygenase Tet1 is highly expressed in the epiblast and yet continues to regulate lineage specification during gastrulation when its expression is diminished. Here, we show how Tet1 plays a pivotal role upstream of germ layer lineage bifurcation. During the transition from naive pluripotency to lineage priming, a global reconfiguration redistributes Tet1 from Oct4-cobound promoters to distal regulatory elements at lineage differentiation genes, which are distinct from high-affinity sites engaged by Oct4. An altered chromatin landscape in Tet1-deficient primed epiblast-like cells is associated with enhanced Oct4 expression and binding to Nodal and Wnt target genes, resulting in collaborative signals that enhance mesendodermal and inhibit neuroectodermal gene expression during lineage segregation. A permissive role for Tet1 in neural fate induction involves Zic2-dependent engagement at neural target genes at lineage priming, is dependent on the signaling environment during gastrulation, and impacts neural tube closure after gastrulation. Our findings provide mechanistic information for epigenetic integration of pluripotency and signal-induced differentiation cues.


Asunto(s)
Diferenciación Celular/genética , Linaje de la Célula/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Células Madre Pluripotentes/citología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Animales , Células Cultivadas , Cromatina/metabolismo , Embrión de Mamíferos , Eliminación de Gen , Regulación del Desarrollo de la Expresión Génica , Estratos Germinativos/metabolismo , Ratones , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Transducción de Señal/genética , Factores de Transcripción/metabolismo
2.
Nucleic Acids Res ; 51(11): 5469-5498, 2023 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-37021585

RESUMEN

Gastrulation begins when the epiblast forms the primitive streak or becomes definitive ectoderm. During this lineage bifurcation, the DNA dioxygenase TET1 has bipartite functions in transcriptional activation and repression, but the mechanisms remain unclear. By converting mouse embryonic stem cells (ESCs) into neuroprogenitors, we defined how Tet1-/- cells switch from neuroectoderm fate to form mesoderm and endoderm. We identified the Wnt repressor Tcf7l1 as a TET1 target that suppresses Wnt/ß-catenin and Nodal signalling. ESCs expressing catalytic dead TET1 retain neural potential but activate Nodal and subsequently Wnt/ß-catenin pathways to generate also mesoderm and endoderm. At CpG-poor distal enhancers, TET1 maintains accessible chromatin at neuroectodermal loci independently of DNA demethylation. At CpG-rich promoters, DNA demethylation by TET1 affects the expression of bivalent genes. In ESCs, a non-catalytic TET1 cooperation with Polycomb represses primitive streak genes; post-lineage priming, the interaction becomes antagonistic at neuronal genes, when TET1's catalytic activity is further involved by repressing Wnt signalling. The convergence of repressive DNA and histone methylation does not inhibit neural induction in Tet1-deficient cells, but some DNA hypermethylated loci persist at genes with brain-specific functions. Our results reveal versatile switching of non-catalytic and catalytic TET1 activities based on genomic context, lineage and developmental stage.


Asunto(s)
5-Metilcitosina , beta Catenina , Animales , Ratones , 5-Metilcitosina/metabolismo , beta Catenina/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Estratos Germinativos/metabolismo , Genómica , Diferenciación Celular/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo
3.
Osteoarthritis Cartilage ; 31(7): 985-994, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37059327

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of the anti-catabolic ADAMTS-5 inhibitor S201086/GLPG1972 for the treatment of symptomatic knee osteoarthritis. DESIGN: ROCCELLA (NCT03595618) was a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 trial in adults (aged 40-75 years) with knee osteoarthritis. Participants had moderate-to-severe pain in the target knee, Kellgren-Lawrence grade 2 or 3 and Osteoarthritis Research Society International joint space narrowing (grade 1 or 2). Participants were randomized 1:1:1:1 to once-daily oral S201086/GLPG1972 75, 150 or 300 mg, or placebo for 52 weeks. The primary endpoint was change from baseline to week 52 in central medial femorotibial compartment (cMFTC) cartilage thickness assessed quantitatively by magnetic resonance imaging. Secondary endpoints included change from baseline to week 52 in radiographic joint space width, Western Ontario and McMaster Universities Osteoarthritis Index total and subscores, and pain (visual analogue scale). Treatment-emergent adverse events (TEAEs) were also recorded. RESULTS: Overall, 932 participants were enrolled. No significant differences in cMFTC cartilage loss were observed between placebo and S201086/GLPG1972 therapeutic groups: placebo vs 75 mg, P = 0.165; vs 150 mg, P = 0.939; vs 300 mg, P = 0.682. No significant differences in any of the secondary endpoints were observed between placebo and treatment groups. Similar proportions of participants across treatment groups experienced TEAEs. CONCLUSIONS: Despite enrolment of participants who experienced substantial cartilage loss over 52 weeks, during the same time period, S201086/GLPG1972 did not significantly reduce rates of cartilage loss or modify symptoms in adults with symptomatic knee osteoarthritis.


Asunto(s)
Osteoartritis de la Rodilla , Adulto , Humanos , Método Doble Ciego , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/tratamiento farmacológico , Dolor/patología , Resultado del Tratamiento
4.
Regul Toxicol Pharmacol ; 145: 105502, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38832926

RESUMEN

Many government agencies and expert groups have estimated a dose-rate of perfluorooctanoate (PFOA) that would protect human health. Most of these evaluations are based on the same studies (whether of humans, laboratory animals, or both), and all note various uncertainties in our existing knowledge. Nonetheless, the values of these various, estimated, safe-doses vary widely, with some being more than 100,000 fold different. This sort of discrepancy invites scrutiny and explanation. Otherwise what is the lay public to make of this disparity? The Steering Committee of the Alliance for Risk Assessment (2022) called for scientists interested in attempting to understand and narrow these disparities. An advisory committee of nine scientists from four countries was selected from nominations received, and a subsequent invitation to scientists internationally led to the formation of three technical teams (for a total of 24 scientists from 8 countries). The teams reviewed relevant information and independently developed ranges for estimated PFOA safe doses. All three teams determined that the available epidemiologic information could not form a reliable basis for a PFOA safe dose-assessment in the absence of mechanistic data that are relevant for humans at serum concentrations seen in the general population. Based instead on dose-response data from five studies of PFOA-exposed laboratory animals, we estimated that PFOA dose-rates 10-70 ng/kg-day are protective of human health.


Asunto(s)
Caprilatos , Relación Dosis-Respuesta a Droga , Fluorocarburos , Cooperación Internacional , Caprilatos/toxicidad , Fluorocarburos/toxicidad , Humanos , Animales , Medición de Riesgo , Contaminantes Ambientales/toxicidad , Exposición a Riesgos Ambientales/efectos adversos
5.
Int Wound J ; 19(8): 2183-2190, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35474634

RESUMEN

Skin-bleaching is a common practice globally and is associated with many cutaneous and systemic health risks. Anecdotally, skin-bleaching is linked to impairments in wound healing, but there are little data to support the claim. This cross-sectional survey of health care professionals serving the Greater Accra Region, Ghana region investigates their observations of wound healing in patients who skin-bleach and their methods for screening skin-bleach use in patients. A 25-item self-administered questionnaire using 5-point Likert scale was distributed with convenient sampling to physicians and nurses employed at Ghanaian hospitals. Fifty-seven electronic and 78 paper responses were collected (total = 135). Most respondents agreed that wounds in skin-bleaching patients heal more slowly (4.22), are more prone to infection (4.11), haemorrhage (3.89), wound dehiscence (3.9), and are more difficult to manage (4.13). No respondent reported universal screening of all patients for skin-bleaching, but most ask about skin-bleaching if there is suspicion of it (42.2%). Our findings support the anecdotes about observable wound healing impairments in patients who skin-bleach. There is also wide variation in skin-bleaching screening practices, suggesting a need for guidelines to properly identify these patients and facilitate early risk prevention.


Asunto(s)
Antiinfecciosos , Cicatrización de Heridas , Humanos , Ghana , Estudios Transversales , Personal de Salud
6.
Regul Toxicol Pharmacol ; 124: 104972, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34119600

RESUMEN

The derivation of Chemical Specific Adjustment Factors (CSAFs) (IPCS, 2005; U.S. EPA, 2014) depends on the choice of appropriate dose metric. EPA and IPCS guidance was applied to derive a CSAF for developmental toxicity for procymidone (PCM). Although kinetic data were not available in humans at any dose, sufficient toxicokinetic data are available in a surrogate species, primates, and from chimeric mice with both rat and human liver cells to offer insights. Alternative approaches were explored in the derivation of the CSAG based on review of the available kinetic data. The most likely dosimetric adjustment is the Cmax based on the character of the critical effect - reduced anogenital distance and increased incidence of hypospadias in male rats, which likely occurs during a small window of time during development of the rat fetus. Cmax is also the default dosimeter from U.S. EPA (1991). However, in this case, the use of Cmax is also likely more conservative than the use of area under the curve (AUC), which otherwise is the default recommendation of the IPCS (2005). Despite human data, estimated tentative CSAF value is 0.48 (range, 0.22 to 0.74). The use of any of these values would be supported by the available data.


Asunto(s)
Compuestos Bicíclicos con Puentes/toxicidad , Desarrollo Fetal/efectos de los fármacos , Fungicidas Industriales/toxicidad , Hipospadias/inducido químicamente , Pruebas de Toxicidad/estadística & datos numéricos , Animales , Área Bajo la Curva , Compuestos Bicíclicos con Puentes/administración & dosificación , Interpretación Estadística de Datos , Femenino , Humanos , Masculino , Toxicocinética
7.
Adv Exp Med Biol ; 1334: 181-204, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34476750

RESUMEN

The anatomical collections at the National Museum of Health and Medicine (NMHM) contain skeletal specimens that highlight the history of military and civilian medicine dating from the American Civil War and the founding of the museum as the Army Medical Museum in 1862. Today, NMHM curates over 6400 gross skeletal specimens consisting primarily of pathological or anomalous single bone elements that display a variety of pathological conditions, including congenital anomalies, neoplasms, healed and unhealed trauma and infectious diseases, and surgical interventions such as amputations and excisions. In an effort to increase accessibility to these pathological specimens, NMHM is collaborating with Virginia Commonwealth University (VCU) and the Laboratory Division of the Federal Bureau of Investigation (FBI) to digitize and disseminate high-quality 3D models via online portals, enabling scholars and educators to manipulate, analyze, and 3D print the models from anywhere in the world. Many institutions with courses in paleopathology and forensic anthropology do not have reference collections or access to museum collections for hands-on teaching. Therefore a digital repository of osteological specimens can provide an unprecedented and unique resource of exemplars for scholars and educators. The sharing of these military medical assets improves historical knowledge and diagnostic capabilities in the fields of medicine and anthropology. This chapter outlines the digitization processes that are being utilized to increase access to these pathological skeletal specimens through multimodal 3D capture.


Asunto(s)
Medicina , Personal Militar , Huesos , Humanos , Laboratorios , Museos
8.
J Oral Maxillofac Surg ; 79(6): 1199-1206, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33647247

RESUMEN

An aerosolizing reducing technique for the extraction of impacted mandibular third molars with the use of a bibevel chisel and mallet will be presented. Every oral and maxillofacial surgeon should have this technique in their armamentarium, especially with the current global pandemic with the severe acute respiratory syndrome coronavirus 2, the cause of coronavirus disease 2019. In this era, we must all consider ways to reduce the number of aerosols produced during the extraction of third molars. Prioritizing hand instrumentation with the use of chisels and mallets will reduce aerosolization as compared with the more traditional technique of using a surgical handpiece.


Asunto(s)
COVID-19 , Diente Impactado , Humanos , Mandíbula , Tercer Molar/cirugía , SARS-CoV-2 , Extracción Dental
9.
Opt Lett ; 45(8): 2331-2334, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32287226

RESUMEN

In this Letter, an enhanced laser speckle optical sensor (LSOS) for nondestructive, noncontact, and high-accuracy strain measurement has been developed. Subsystems of laser beam shaping and telecentric imaging were incorporated into the LSOS to achieve optimized speckle patterns, and a field-of-view (FOV) separation was introduced to extend sensor gauge length. Validation tests confirmed that the LSOS achieved consistent results with resistive strain gauges in laboratory conditions with maximum RMS error (RMSE) of $ 9.44\;\unicode{x00B5} \unicode{x03B5} $9.44µÎµ. Sensing practicality was demonstrated in field tests. The results showed that the LSOS is capable of achieving accurate strain measurements in an external environment with maximum RMSE of $ 13.34\;\unicode{x00B5}\unicode{x03B5} $13.34µÎµ.

10.
Int J Syst Evol Microbiol ; 70(5): 3534-3540, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32375937

RESUMEN

Seven strains of an unidentifiable Corynebacterium species recovered from blood cultures, urine or cerebrospinal fluid over 26 years, closest to but differentiated from Corynebacterium imitans by 16S rRNA gene and partial rpoB gene sequencing, were studied. In November 2017, Atasayar et al. described a blood culture isolate as Corynebacterium gottingense sp. nov., which had >99 % similarity by 16S rRNA gene sequencing to the Canadian strains. In January 2018, Jani et al. described Corynebacterium godavarianum sp. nov., recovered from the Godavari River, India, which also had >99 % similarity by 16S/rpoB sequencing to the Canadian strains and C. gottingense. In May 2018, Wei et al. described Corynebacterium hadale recovered from hadopelagic water; this too had >99 % similarity by 16S rRNA gene sequencing to C. gottingense, C. godavarianum and the Canadian strains. C. gottingense DSM 103494T and C. godavarianum LMG 29598T were acquired and whole genome sequencing was performed (not previously done). Results were compared with genomes from C. hadale (GenBank accession NQMQ01) and the Canadian isolates. We found that these ten genomes formed a single taxon when compared using digital DNA-DNAhybridization, average nucleotide identity using blastn and average amino acid identity criteria but exhibited some subtle biochemical and chemotaxonomic differences. Heuristically, we propose that C. godavarianum and C. hadale are later heterotypic synonyms of, and the Canadian isolates are identifiable as, C. gottingense. We provide an emended description of Corynebacterium gottingense Atasayar et al. 2017; genomes ranged from 2.48 to 2.69 Mb (C. gottingense DSM 103494T, 2.62 Mb) with G+C content of 65.1-65.6 mol% (WGS), recovered from clinical and environmental sites.


Asunto(s)
Corynebacterium/clasificación , Filogenia , Técnicas de Tipificación Bacteriana , Composición de Base , Canadá , ADN Bacteriano/genética , Genes Bacterianos , Humanos , India , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
11.
Int J Syst Evol Microbiol ; 70(1): 83-88, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31596191

RESUMEN

Auritidibacter ignavus is a Gram-stain-positive bacillus derived from otorrhea. Four strains derived from ear discharges in Canada and Switzerland, with features consistent with but distinguishable from Auritidibacter ignavus IMMIB L-1656T (accession number FN554542) by 16S rRNA gene sequencing (97.5 % similarity), were thought to represent a novel species of the genus Auritidibacter. Auritidibacter ignavus DSM 45359T (=IMMIB L-1656T) was acquired to compare with Canadian and Swiss strains by whole-genome sequencing (WGS). Unexpectedly, those isolates were observed to be consistent with A. ignavus DSM 45359T by WGS (ANIb scores >98 %), MALDI-TOF (Bruker), cellular fatty acid analysis and biochemically (some differences were observed). A nearly full 16S rRNA gene sequence could not be readily prepared from A. ignavus DSM 45359T, even after multiple attempts. A 16S rRNA gene chimeric consensus sequence created from the genome assembly of A. ignavus DSM 45359T had only 97.5 % similarity to that of A. ignavus IMMIB L-1656T, implying that 16S rRNA sequence accession number FN554542 could not be replicated. We concluded that our isolates of members of the genus Auritidibacter were consistent with A. ignavus DSM 45359T, did not represent a novel species, and that the sequence corresponding to FN554542 was not reproducible. By WGS, A. ignavus DSM 45359T had genome of 2.53×106 bp with a DNA G+C content of 59.34%, while genomes of Canadian and Swiss isolates ranged from 2.47 to 2.59×106 bp with DNA G+C contents of 59.3-59.52 %. A. ignavus NML 100628 (=NCTC 14178=LMG 30897) did not demonstrate a rodcoccus cycle. Emendation of Auritidibacter ignavus was proposed based on these results.


Asunto(s)
Micrococcaceae/clasificación , Filogenia , Anciano , Técnicas de Tipificación Bacteriana , Composición de Base , Canadá , ADN Bacteriano/genética , Oído/microbiología , Ácidos Grasos/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Suiza
12.
Virus Genes ; 56(1): 95-98, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31654295

RESUMEN

To date, only two rodent-borne hantaviruses have been detected in sub-Saharan Africa. Here, we report the detection of a yet unknown hantavirus in a Natal mastomys (Mastomys natalensis) in Méliandou, Guinea, in 2014. The phylogenetic placement of this virus suggests that it might represent a cross-order spillover event from an unknown bat or eulipotyphlan host.


Asunto(s)
Infecciones por Hantavirus/veterinaria , Murinae/virología , Orthohantavirus/aislamiento & purificación , Enfermedades de los Roedores/virología , Animales , Guinea , Orthohantavirus/clasificación , Orthohantavirus/genética , Infecciones por Hantavirus/virología , Filogenia
13.
J Phys Chem A ; 122(46): 9065-9072, 2018 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-30380860

RESUMEN

The bonding preferences in the mixed dihalides (MXY) of groups 2 and 12 metals, including the extent of any anomalous bending, are assessed and established. The deviation from linearity in group 2 metal binary dihalides is well-known, runs contrary to simple bonding models, and is believed to be decisive for structural preferences in the extended solids. Yet the bonding in the ternary, MXY, molecules has not been investigated systematically until now. The structure and bonding in these ternary systems (and, for completeness, the binary cases as well) are determined herein at high levels of theory. A softness criterion formulated by Szentpály and Schwerdtfeger, and tested initially on binary dihalides with predictions for mixed systems, is confirmed to apply broadly for binary and ternary species of the group 2 and 12 metals. For each M, a function of the form E(Θ) = Ae- kΘ is shown to predict the barriers to linearization for all of the bent molecules. The extended solids of some of the ternary dihalides are of interest for their optical properties. The bonding in the molecular (MXY) units may offer we think some new perspectives from which to rationalize the bonding preferences in those crystal structures.

14.
Malar J ; 15(1): 486, 2016 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-27653949

RESUMEN

BACKGROUND: Malaria, a disease caused by protozoan parasites of the genus Plasmodium and transmitted by female anopheline mosquitoes, is a major cause of morbidity, mortality and loss in productivity in humans. Baringo County is prone to seasonal transmissions of malaria mostly in the rainy seasons. METHODS: This cross-sectional study used a mixed methods approach to collect data on knowledge and lay management of malaria. A questionnaire survey was administered to 560 respondents while qualitative data was collected through 20 focus group discussions in four ecological zones covering Baringo North, Baringo South and Marigat sub-Counties of Baringo County. Analyses were done through summary and inferential statistics for quantitative data and content analysis for qualitative data. RESULTS: The study communities were knowledgeable of malaria signs, symptoms, cause and seasonality but this biomedical knowledge co-existed with other local perceptions. This knowledge, however, did not influence their first (p = 0.77) or second choice treatments (p = 0.49) and compliance to medication (p = 0.84). Up to 88 % of respondents reported having suffered from malaria. At the onset of a suspected malaria case community members reported the following: 28.9 % visited a health facility, 37.2 % used analgesics, 26.6 % herbal treatments, 2.2 % remnant malaria medicines, 2.2 % over the counter malaria medicines, 1 % traditional healers and 1.8 % other treatments. Nearly all respondents (97.8 %) reported visiting a health facility for subsequent treatments. Herbal treatments comprised of infusions and decoctions derived from roots, barks and leaves of plants believed to have medicinal value. Compliance to conventional malaria treatment regime was, however, identified as a challenge in malaria management. Quick relief from symptoms, undesirable qualities like drug bitterness and bad smell, undesirable side-effects, such as nausea and long regimen of treatment were some of the contributors to non-compliance. Men and women exhibited different health-seeking behaviours based on the cultural expectations of masculinity, femininity, gender roles and acceptability of health services. CONCLUSIONS: While knowledge of malaria is important in identifying the disease, it does not necessarily lead to good management practice. Treatment-seeking behaviour is also influenced by perceived cause, severity of disease, timing, anticipated cost of seeking treatment and gender, besides the availability of both traditional and conventional medicines.

15.
BMC Public Health ; 16: 32, 2016 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-26762147

RESUMEN

BACKGROUND: Human behavioral factors have been found to be central in the transmission of Rift Valley fever. Consumption of contaminated meat and milk in particular have been identified as one of the key risk factors for the transmission of Rift Valley fever in humans. In pastoral communities, livestock is the main source of livelihood from which many benefits such as food as well as economic and cultural services are derived. Zoonotic diseases therefore have a great impact on pastoral communities livelihoods. However, lay perceptions regarding the transmission of these diseases including Rift Valley fever hampers their effective control. This study investigated the lay perceptions of risks for Rift Valley fever transmission in a pastoral community in northeastern Kenya. METHODS: A qualitative study was carried out in Ijara district, Kenya which was one of the hotspots of Rift Valley during the 2006/2007 outbreak. Data were collected using focus group discussions and narratives guided by checklists. Eight focus group discussions consisting of 83 participants and six narratives were conducted. Data was transcribed, coded and analysed according to Emergent themes. RESULTS: The participants reported that they had experienced Rift Valley fever in their livestock especially sheep and in humans both in 1997/1998 and 2006/2007. However, they believed that infections in humans occurred as a result of mosquito bites and had little to do with their consumption of meat, milk and blood from infected livestock. The participants in this study indicated that they had heard of the risks of acquiring the disease through consumption of livestock products but their experiences did not tally with the information they had received hence to them, Rift Valley fever was not transmissible through their dietary practices. CONCLUSIONS: Though the communities in this region were aware of Rift Valley fever, they did not have elaborate information regarding the disease transmission dynamics to humans. To avoid misconception about transmission of the disease, intervention strategies, require to be accompanied by comprehensive explanations of the dynamics of its transmission. It is necessary to develop appropriate interventions that take into consideration, lay perceptions of risk factors for the disease and communities' livelihood strategies.


Asunto(s)
Dieta , Conducta Alimentaria , Conocimientos, Actitudes y Práctica en Salud , Ganado/virología , Fiebre del Valle del Rift/transmisión , Zoonosis , Adolescente , Adulto , Animales , Brotes de Enfermedades , Femenino , Humanos , Kenia/epidemiología , Masculino , Carne/virología , Persona de Mediana Edad , Leche/virología , Características de la Residencia , Fiebre del Valle del Rift/epidemiología , Fiebre del Valle del Rift/etiología , Fiebre del Valle del Rift/virología , Factores de Riesgo , Población Rural , Ovinos/virología , Adulto Joven , Zoonosis/epidemiología
16.
Regul Toxicol Pharmacol ; 80: 125-33, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27346665

RESUMEN

A method for determining a safety range for non-cancer risks is proposed, similar in concept to the range used for cancer in the management of waste sites. This safety range brings transparency to the chemical specific Reference Dose or Concentration by replacing their "order of magnitude" definitions with a scientifically-based range. EPA's multiple RfCs for trichloroethylene (TCE) were evaluated as a case study. For TCE, a multi-endpoint safety range was judged to be 3 µg/m(3) to 30 µg/m,(3) based on a review of kidney effects found in NTP (1988), thymus effects found in Keil et al. (2009) and cardiac effects found in the Johnson et al. (2003) study. This multi-endpoint safety range is derived from studies for which the appropriate averaging time corresponds to different exposure durations, and, therefore, can be applied to both long- and short-term exposures with appropriate consideration of exposure averaging times. For shorter-term exposures, averaging time should be based on the time of cardiac development in humans during fetal growth, an average of approximately 20-25 days.


Asunto(s)
Monitoreo del Ambiente/métodos , Contaminantes Ambientales/efectos adversos , Sitios de Residuos Peligrosos , Residuos Peligrosos/efectos adversos , Tricloroetileno/efectos adversos , Animales , Técnicas de Apoyo para la Decisión , Relación Dosis-Respuesta a Droga , Monitoreo del Ambiente/normas , Contaminantes Ambientales/análisis , Residuos Peligrosos/análisis , Humanos , Exposición por Inhalación/efectos adversos , Valores de Referencia , Medición de Riesgo , Administración de la Seguridad , Factores de Tiempo , Pruebas de Toxicidad , Tricloroetileno/análisis
17.
Regul Toxicol Pharmacol ; 73(3): 903-13, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26416168

RESUMEN

Asthma is a complex syndrome with significant consequences for those affected. The number of individuals affected is growing, although the reasons for the increase are uncertain. Ensuring the effective management of potential exposures follows from substantial evidence that exposure to some chemicals can increase the likelihood of asthma responses. We have developed a safety assessment approach tailored to the screening of asthma risks from residential consumer product ingredients as a proactive risk management tool. Several key features of the proposed approach advance the assessment resources often used for asthma issues. First, a quantitative health benchmark for asthma or related endpoints (irritation and sensitization) is provided that extends qualitative hazard classification methods. Second, a parallel structure is employed to include dose-response methods for asthma endpoints and methods for scenario specific exposure estimation. The two parallel tracks are integrated in a risk characterization step. Third, a tiered assessment structure is provided to accommodate different amounts of data for both the dose-response assessment (i.e., use of existing benchmarks, hazard banding, or the threshold of toxicological concern) and exposure estimation (i.e., use of empirical data, model estimates, or exposure categories). Tools building from traditional methods and resources have been adapted to address specific issues pertinent to asthma toxicology (e.g., mode-of-action and dose-response features) and the nature of residential consumer product use scenarios (e.g., product use patterns and exposure durations). A case study for acetic acid as used in various sentinel products and residential cleaning scenarios was developed to test the safety assessment methodology. In particular, the results were used to refine and verify relationships among tiered approaches such that each lower data tier in the approach provides a similar or greater margin of safety for a given scenario.


Asunto(s)
Ácido Acético/efectos adversos , Asma/inducido químicamente , Seguridad de Productos para el Consumidor , Productos Domésticos/efectos adversos , Irritantes/efectos adversos , Pulmón/efectos de los fármacos , Pruebas de Toxicidad/métodos , Animales , Asma/diagnóstico , Asma/fisiopatología , Benchmarking , Relación Dosis-Respuesta a Droga , Determinación de Punto Final , Exposición a Riesgos Ambientales/efectos adversos , Humanos , Pulmón/fisiopatología , Modelos Teóricos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Pruebas de Toxicidad/normas
18.
Regul Toxicol Pharmacol ; 73(1): 248-64, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26212636

RESUMEN

Ethanol-based topical antiseptic hand rubs, commonly referred to as alcohol-based hand sanitizers (ABHS), are routinely used as the standard of care to reduce the presence of viable bacteria on the skin and are an important element of infection control procedures in the healthcare industry. There are no reported indications of safety concerns associated with the use of these products in the workplace. However, the prevalence of such alcohol-based products in healthcare facilities and safety questions raised by the U.S. FDA led us to assess the potential for developmental toxicity under relevant product-use scenarios. Estimates from a physiologically based pharmacokinetic modeling approach suggest that occupational use of alcohol-based topical antiseptics in the healthcare industry can generate low, detectable concentrations of ethanol in blood. This unintended systemic dose probably reflects contributions from both dermal absorption and inhalation of volatilized product. The resulting internal dose is low, even under hypothetical, worst case intensive use assumptions. A significant margin of exposure (MOE) exists compared to demonstrated effect levels for developmental toxicity under worst case use scenarios, and the MOE is even more significant for typical anticipated occupational use patterns. The estimated internal doses of ethanol from topical application of alcohol-based hand sanitizers are also in the range of those associated with consumption of non-alcoholic beverages (i.e., non-alcoholic beer, flavored water, and orange juice), which are considered safe for consumers. Additionally, the estimated internal doses associated with expected exposure scenarios are below or in the range of the expected internal doses associated with the current occupational exposure limit for ethanol set by the Occupational Safety and Health Administration. These results support the conclusion that there is no significant risk of developmental or reproductive toxicity from repeated occupational exposures and high frequency use of ABHSs or surgical scrubs. Overall, the data support the conclusion that alcohol-based hand sanitizer products are safe for their intended use in hand hygiene as a critical infection prevention strategy in healthcare settings.


Asunto(s)
Antiinfecciosos Locales/efectos adversos , Etanol/efectos adversos , Exposición Profesional/efectos adversos , Administración por Inhalación , Administración Tópica , Animales , Haplorrinos , Personal de Salud , Humanos , Ratas , Medición de Riesgo , Seguridad , Absorción Cutánea/fisiología
19.
J Clin Microbiol ; 52(9): 3180-3, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24951802

RESUMEN

The species Corynebacterium pyruviciproducens was described in 2010 based on the features of a single strain. In this report, we describe the chemotaxonomic and phenotypic characteristics of 11 C. pyruviciproducens clinical strains isolated in Switzerland and Canada in comparison to the strain 06-17730(T). Heterogeneities within the type strain were found in the 16S rRNA gene and in biochemical markers. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identification of this species could not be achieved since currently this bacterial species is not included in the corresponding database. Reliable identification is obtained only with sequence-based identification tools. Results of antimicrobial susceptibility testing of this species with an extended panel of antimicrobials are presented here for the first time.


Asunto(s)
Infecciones por Corynebacterium/microbiología , Corynebacterium/clasificación , Corynebacterium/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Canadá , Análisis por Conglomerados , Corynebacterium/genética , Corynebacterium/fisiología , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Humanos , Datos de Secuencia Molecular , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Suiza
20.
Heliyon ; 10(4): e25672, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38379978

RESUMEN

Considering procurement process performance assessment, measurement systems such as balance scorecard and capability maturity models are used to assess procurement performance to give a reasonable indication of actual performance. These tools are ideal for practical applications that depend on other performance criteria but are short of comparing planned to actual timelines set for procurement processes. This fosters persistent delays in public procurement. Six Sigma implementation benefits including addressing process delays have fostered its implementation for service improvements. Unfortunately, Six Sigma implementation in public procurement is very rare largely due to its expensive nature. The objective of this study is to develop a Procurement Delay Index (PDindex): a performance measure in the context of a Six Sigma methodology that provides a specific value to describe the delays in the procurement process. To enhance uniformity in performance measurement of process timeliness, a rating scale for determining the timeliness of the procurement process is proposed. A practical demonstration of the application of PDindex for use by procurement professionals is also presented. PDindex serves as a standard by which to determine procurement processes' timeliness and is less expensive to implement. A PDindex of 3σ has been recommended as the acceptable limit for procurement process delays.

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