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1.
Clin Neuropsychol ; 38(3): 683-714, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-37674299

RESUMEN

ObjectiveOlder individuals face a higher likelihood of developing dementia. The rate of cognitive decline resulting from dementia is not equivalent for all, as some patients with dementia are able to function independently longer than others, despite having similar disease burden. The cognitive reserve (CR) theory provides one explanation for the differing rate of decline. CR suggests that there are factors-most notably, educational attainment and occupational attainment-that can protect against the cognitive decline. Although the beneficial effects of these notable CR factors are clear, not all are easily modifiable. Participation in leisure activities may represent a more easily modifiable factor. Some research hints at beneficial effects of leisure activities, although specific leisure activities have not been well examined. The present study examined the relations between handicraft art leisure activities (HALAs) and multiple cognitive domains. MethodArchival WAIS-IV and demographic data for 50 California retirement community residents were examined. ResultsHALA participation accounted for statistically significant variance in working memory performance (R2 = .40, ß = .24%) over and above the established CR factors of age, depression, educational attainment, and occupational attainment. In addition, HALA participation was related to a better ability to perform abstract visual information tasks (Block Design subtest, r = .28, p = .05) and non-verbal reasoning tasks (Visual Puzzles subtest, r = .38, p = .008). ConclusionsHALA participation among older adults could contribute to the retention of cognitive function, supporting the role of HALA participation as a CR factor.


Asunto(s)
Disfunción Cognitiva , Reserva Cognitiva , Demencia , Humanos , Anciano , Pruebas Neuropsicológicas , Cognición , Actividades Recreativas/psicología
2.
Food Chem Toxicol ; 184: 114352, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38081535

RESUMEN

4-(2-Hydroxyethyl) morpholine (HEM) is widely used as a building block of macromolecules in the manufacture of pharmaceuticals and dietary supplements and could remain as an impurity in the finished products. An evaluation of HEM was conducted to identify endpoints that could be used to determine the point-of-departure (POD) for use in assessing the potential risk from exposure to HEM. No oral repeated dose toxicological studies of appropriate duration were found for HEM. Therefore, suitable analogue(s) were identified. Although oral repeated dose studies were available for the analogues, the studies were not of sufficient duration for use in the assignment of a POD for risk evaluation. Accordingly, the Threshold of Toxicological Concern (TTC) approach, which proposes that a de minimis value can be derived to qualitatively assess risk, was considered for HEM. To determine the appropriate TTC approach (genotoxic or non-genotoxic), the genotoxicity of HEM and its analogues were evaluated. The weight of the evidence indicated that HEM, and the appropriate analogues, are not genotoxic. Considering the chemical structure of HEM, the non-genotoxic Cramer class III TTC value of 1.5 µg/kg bw/day was determined to be appropriate for use in safety assessment of HEM as an impurity in products intended for human consumption.


Asunto(s)
Daño del ADN , Suplementos Dietéticos , Humanos , Medición de Riesgo , Suplementos Dietéticos/toxicidad , Morfolinas/toxicidad , Preparaciones Farmacéuticas
3.
Toxicology ; 501: 153714, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38141718

RESUMEN

For genotoxic carcinogens, covalent binding to DNA is a critical initiating event in tumorigenesis. The present research investigated dose-effect relationships of three genotoxic carcinogens representing different structural classes, 2-acetylaminofluorene (2-AAF), benzo[a]pyrene (B[a]P) and quinoline (QUI), to assess the existence of no-observed-effect-levels (NOELs) for the formation of DNA adducts. Carcinogens were administered into the air sac of fertilized turkey eggs over wide dose ranges in three daily injections on days 22 to 24 of incubation. DNA adducts were measured in the fetal turkey livers by the 32P-nucleotide postlabeling (NPL) assay. B[a]P and QUI produced DNA adducts in a dosage-related manner and exhibited NOELs at 0.65 and 0.35 mg/kg bw/day, respectively. In contrast, 2-AAF formed DNA adducts at all tested dosages down to 0.005 mg/kg bw/day. Benchmark dose (BMD) analysis identified the potencies of 2-AAF and QUI to be similar, while B[a]P was the least potent compound. Overall, findings in fetal turkey livers demonstrated that exposure levels to genotoxic compounds that do not result in DNA adducts can exist but are not evident with all carcinogens of this type. The use of mechanistic dose-effect studies for genotoxic endpoints can provide critical information for prioritization of concerns for risk assessment.


Asunto(s)
Carcinógenos , Aductos de ADN , Carcinógenos/metabolismo , Aductos de ADN/metabolismo , Hígado , Daño del ADN , 2-Acetilaminofluoreno/farmacología , 2-Acetilaminofluoreno/toxicidad
4.
Biol Reprod ; 109(6): 892-903, 2023 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-37698264

RESUMEN

Perinatal nutrition modulates the hypothalamic neurocircuitries controlling GnRH release, thus programming pubertal maturation in female mammals. Objectives of experiments reported here were to test the hypotheses that prenatal nutrition during mid- to late gestation interacts with postnatal nutrition during the juvenile period in heifer offspring to alter expression of leptin receptor (LepR) variants (ObRa, ObRb, ObRc, ObRt), and lipoprotein transporter molecules (LRP1 and 2) in the choroid plexus, leptin transport across the blood-brain barrier, and hypothalamic-hypophyseal responsiveness to exogenous ovine leptin (oleptin) during fasting. Nutritional programming of heifers employed a 3 × 2 factorial design of maternal (high, H; low, L; and moderate, M) × postnatal (H and L) dietary treatments. Results (Expt. 1) demonstrated that prepubertal heifers born to L dams, regardless of postnatal diet, had reduced expression of the short isoform of ObRc compared to H and M dams, with sporadic effects of undernutrition (L or LL) on ObRb, ObRt, and LRP1. Intravenous administration of oleptin to a selected postpubertal group (HH, MH, LL) of ovariectomized, estradiol-implanted heifers fasted for 56 h (Expt. 2) did not create detectable increases in third ventricle cerebrospinal fluid but increased gonadotropin secretion in all nutritional groups tested. Previous work has shown that leptin enhances gonadotropin secretion during fasting via effects at both hypothalamic and anterior pituitary levels in cattle. Given the apparent lack of robust transfer of leptin across the blood-brain barrier in the current study, effects of leptin at the adenohypophyseal level may predominate in this experimental model.


Asunto(s)
Leptina , Receptores de Leptina , Femenino , Animales , Bovinos , Ovinos , Embarazo , Leptina/genética , Leptina/farmacología , Leptina/metabolismo , Receptores de Leptina/genética , Estado Nutricional , Gonadotropinas/metabolismo , Dieta , Mamíferos/metabolismo
5.
J Paediatr Child Health ; 59(2): 307-318, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36537724

RESUMEN

AIM: The purpose of this study was to evaluate whether pre-recorded video-based lectures (VBLs) covering a range of paediatric topics are an acceptable means of providing ongoing education for consultant and trainee paediatricians in Australia. METHODS: Previous participants (paediatric consultants and junior medical officers) of a neurology outreach teleconference programme offered by a paediatric neurologist between 2017 and 2020 were invited to participate in a multi-specialty pre-recorded video-based education programme. Acceptability was explored by assessing relevance, likelihood of utilising VBL's in the future, uptake and learning activity preferences. The impact of VBLs on confidence, currency and practice was also explored. Additional data including topics of interest, preferred video format, duration, viewing method and frequency of delivery were captured, to better understand participant preferences to inform future efforts. RESULTS: A total of 135 consented; 116 returned baseline; 94 returned follow-up surveys. Preferred learning activities included a live/interactive component. Videos were considered relevant. Preferences for pre-recorded videos improved from ninth to sixth most preferred learning activity post-intervention. VBL convenience and accessibility were valued. Practice was altered in: approach to management, use of treatments, confidence in decision-making, and discussion with families and patients. The average view duration was 16 min. Longer videos yielded slightly lower audience retention rates. For future offerings, the majority endorsed a preference for a 'mixed' video format and duration of 20-40 min, offered monthly. CONCLUSION: Video-based medical education is an appealing and sustainable alternative, given the convenience of unrestricted accessibility, in meeting ongoing learning needs of Australian paediatricians and trainees.


Asunto(s)
Personal de Salud , Aprendizaje , Humanos , Niño , Australia , Personal de Salud/educación , Encuestas y Cuestionarios , Pediatras
6.
Foods ; 11(18)2022 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-36140952

RESUMEN

Commonly consumed foods and beverages can contain chemicals with reported carcinogenic activity in rodent models. Moreover, exposures to some of these substances have been associated with increased cancer risks in humans. Food-borne carcinogens span a range of chemical classes and can arise from natural or anthropogenic sources, as well as form endogenously. Important considerations include the mechanism(s) of action (MoA), their relevance to human biology, and the level of exposure in diet. The MoAs of carcinogens have been classified as either DNA-reactive (genotoxic), involving covalent reaction with nuclear DNA, or epigenetic, involving molecular and cellular effects other than DNA reactivity. Carcinogens are generally present in food at low levels, resulting in low daily intakes, although there are some exceptions. Carcinogens of the DNA-reactive type produce effects at lower dosages than epigenetic carcinogens. Several food-related DNA-reactive carcinogens, including aflatoxins, aristolochic acid, benzene, benzo[a]pyrene and ethylene oxide, are recognized by the International Agency for Research on Cancer (IARC) as causes of human cancer. Of the epigenetic type, the only carcinogen considered to be associated with increased cancer in humans, although not from low-level food exposure, is dioxin (TCDD). Thus, DNA-reactive carcinogens in food represent a much greater risk than epigenetic carcinogens.

7.
Int J Toxicol ; 41(4): 297-311, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35658642

RESUMEN

DNA damage is an established initiating event in the mutagenicity and carcinogenicity of genotoxic chemicals. Accordingly, assessment of this endpoint is critical for chemicals which are being developed for use in humans. To assess the ability of the Chicken Egg Genotoxicity Assay (CEGA) to detect genotoxic pharmaceuticals, a set of 23 compounds with different pharmacological and reported genotoxic effects was tested for the potential to produce nuclear DNA adducts and strand breaks in the embryo-fetal livers using the 32P-nucleotide postlabeling (NPL) and comet assays, respectively. Due to high toxicity, two aneugens, colchicine and vinblastine, and an autophagy inhibitor, hydroxychloroquine, could not be evaluated. Out of the 20 remaining pharmaceuticals, 10 including estrogen modulators, diethylstilbestrol and tamoxifen, antineoplastics cyclophosphamide, etoposide, and mitomycin C, antifungal griseofulvin, local anesthetics lidocaine and prilocaine, and antihistamines diphenhydramine and doxylamine, yielded clear positive outcomes in at least one of the assays. The antihypertensive vasodilator hydralazine and antineoplastics streptozotocin and teniposide, produced only DNA strand breaks, which were not dose-dependent, and thus, the results with these 3 pharmaceuticals were considered equivocal. No DNA damage was detected for 7 compounds, including the purine antagonist 6-thioguanine, antipyretic analgesics acetaminophen and phenacetin, antibiotic ciprofloxacin, antilipidemic clofibrate, anti-inflammatory ibuprofen, and sedative phenobarbital. However, low solubility of these compounds limited dosages tested in CEGA. Overall, results in CEGA were largely in concordance with the outcomes in other systems in vitro and in vivo, indicating that CEGA provides reliable detection of DNA damaging activity of genotoxic compounds. Further evaluations with a broader set of compounds would support this conclusion.


Asunto(s)
Pollos , Daño del ADN , Animales , Ensayo Cometa/métodos , Aductos de ADN , Humanos , Pruebas de Mutagenicidad/métodos , Mutágenos/toxicidad , Preparaciones Farmacéuticas
8.
Biol Reprod ; 107(4): 1035-1045, 2022 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-35703941

RESUMEN

Objectives were to test the hypothesis that pre- and post-natal nutrition in the bovine female, independently or interactively, affect age at puberty and functional characteristics of the estrous cycle of sexually mature offspring. Brangus and Braford (n = 97) beef cows bearing a female fetus were fed to achieve body condition scores of 7.5-8 (H, obese), 5.5-6 (M, moderate), or 3-3.5 (L, thin) by the start of the third trimester and maintained until parturition. Heifer offspring were weaned and fed to gain weight at either a high (H; 1 kg/day) or a low (L; 0.5 kg/day) rate between 4 and 8 months of age, then fed the same diet during a common feeding period until puberty, which resulted in compensatory growth of heifers in the L group. Heifers (n = 95) from the H postnatal diet reached puberty 2 months earlier (12 ± 0.4 months; P = 0.0002) than those from the L postnatal diet (14 ± 0.4 months). Estrous cycles of a subgroup of postpubertal heifers (n = 53) were synchronized to evaluate antral follicle count (AFC), rate of growth and size of the pre-ovulatory follicle, size of corpus luteum and ovary, endometrial thickness, and plasma concentrations of progesterone and estradiol-17ß (E2). Although there was a trend for postnatal H heifers to have greater AFC and plasma concentrations of E2 compared to L heifers, neither pre- nor post-natal nutrition affected any other physiological or hormonal variables, including short-term fertility. Postnatal nutritional effects on pubertal age remained the dominant observed feature.


Asunto(s)
Progesterona , Maduración Sexual , Animales , Bovinos , Cuerpo Lúteo , Dieta/veterinaria , Estradiol , Femenino , Folículo Ovárico/fisiología , Embarazo , Maduración Sexual/fisiología
9.
Mutagenesis ; 37(1): 13-23, 2022 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-35302169

RESUMEN

BlueScreen HC is a mammalian cell-based assay for measuring the genotoxicity and cytotoxicity of chemical compounds and mixtures. The BlueScreen HC assay has been utilized at the Research Institute for Fragrance Materials in a safety assessment program as a screening tool to prioritize fragrance materials for higher-tier testing, as supporting evidence when using a read-across approach, and as evidence to adjust the threshold of toxicological concern. Predictive values for the BlueScreen HC assay were evaluated based on the ability of the assay to predict the outcome of in vitro and in vivo mutagenicity and chromosomal damage genotoxicity assays. A set of 371 fragrance materials was assessed in the BlueScreen HC assay along with existing or newly generated in vitro and in vivo genotoxicity data. Based on a weight-of-evidence approach, the majority of materials in the data set were deemed negative and concluded not to have the potential to be genotoxic, while only a small proportion of materials were determined to show genotoxic effects in these assays. Analysis of the data set showed a combination of high positive agreement but low negative agreement between BlueScreen HC results, in vitro regulatory genotoxicity assays, and higher-tier test results. The BlueScreen HC assay did not generate any false negatives, thereby providing robustness when utilizing it as a high-throughput screening tool to evaluate the large inventory of fragrance materials. From the perspective of protecting public health, it is desirable to have no or minimal false negatives, as a false-negative result may incorrectly indicate the lack of a genotoxicity hazard. However, the assay did have a high percentage of false-positive results, resulting in poor positive predictivity of the in vitro genotoxicity test battery outcome. Overall, the assay generated 100% negative predictivity and 3.9% positive predictivity. In addition to the data set of 371 fragrance materials, 30 natural complex substances were evaluated for BlueScreen HC, Ames, and in vitro micronucleus assay, and a good correlation in all three assays was observed. Overall, while a positive result may have to be further investigated, these findings suggest that the BlueScreen HC assay can be a valuable screening tool to detect the genotoxic potential of fragrance materials and mixtures.


Asunto(s)
Daño del ADN , Odorantes , Animales , Bioensayo/métodos , Mamíferos , Pruebas de Mutagenicidad/métodos , Mutágenos/toxicidad
10.
Genetics ; 220(4)2022 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-35134929

RESUMEN

WormBase (www.wormbase.org) is the central repository for the genetics and genomics of the nematode Caenorhabditis elegans. We provide the research community with data and tools to facilitate the use of C. elegans and related nematodes as model organisms for studying human health, development, and many aspects of fundamental biology. Throughout our 22-year history, we have continued to evolve to reflect progress and innovation in the science and technologies involved in the study of C. elegans. We strive to incorporate new data types and richer data sets, and to provide integrated displays and services that avail the knowledge generated by the published nematode genetics literature. Here, we provide a broad overview of the current state of WormBase in terms of data type, curation workflows, analysis, and tools, including exciting new advances for analysis of single-cell data, text mining and visualization, and the new community collaboration forum. Concurrently, we continue the integration and harmonization of infrastructure, processes, and tools with the Alliance of Genome Resources, of which WormBase is a founding member.


Asunto(s)
Caenorhabditis , Nematodos , Animales , Caenorhabditis/genética , Caenorhabditis elegans/genética , Bases de Datos Genéticas , Genoma , Genómica , Humanos , Nematodos/genética
11.
Food Chem Toxicol ; 159: 112659, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34801651

RESUMEN

Mintlactone (chemical name 3,6-dimethyl-5,6,7,7a-tetrahydro-1-benzofuran-2(4H)-one, CAS Number 13341-72-5) is a fragrance and flavor ingredient with reported uses in many different cosmetics, personal care, and household products. In order to evaluate the genotoxic potential of mintlactone, in vitro and in vivo genotoxicity tests were conducted. Results from bacterial mutagenicity tests varied across different batches of differing purity with positive results observed in TA98 only. An in vivo comet assay was also considered to be positive in livers of female mice but negative in male mice. In contrast, in vitro and in vivo micronucleus tests, as well as 3D skin comet/micronucleus tests, were negative, indicating no chromosomal or DNA damage. The underlying causes for these contradictory results are not clear. It appears that the purity and/or stability of the test material may be an issue. In the absence of dependable scientific information on the purity and/or storage stability of mintlactone, its safety for use as a fragrance ingredient cannot be substantiated.


Asunto(s)
Daño del ADN/efectos de los fármacos , Lactonas/toxicidad , Mutágenos/toxicidad , Terpenos/toxicidad , Animales , Ensayo Cometa , Femenino , Aromatizantes , Masculino , Ratones , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Perfumes
12.
Crit Rev Toxicol ; 51(7): 600-621, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34756157

RESUMEN

Traditionally, human health risk assessment focuses on defining the hazard through mammalian toxicity studies followed by exposure estimation. We have explored ways of predicting exposure based primarily on the use scenario and comparing the exposure to reference dose values derived by various regulatory agencies (US EPA, JMPR, and EU Commission) in order to identify mammalian toxicity studies that are relevant to human health risk assessment. Human dietary exposure was based on existing residue data for substances with comparable use on the same or similar crops. Human occupational exposures were based on the use scenarios and application methods. To provide a point of comparison for the exposure predictions, data were collated for acute, chronic and occupational reference dose values derived by various regulatory agencies (US EPA, JMPR, and EU Commission). The exposure predictions and range of hazard endpoints were compared using the ILSI HESI Risk21 risk matrix plots in order to visualise and contextualise the level of potential concern for the exposure prediction. In addition, an approach is proposed to categorise the likelihood of acceptability of risk based on where the exposure sits relative to the distribution of reference dose values. The approaches proposed in this study allow for exposure prediction based on the Good Agricultural Practice (GAP) in conjunction with the use of existing hazard data for crop protection products in order to make an initial determination on acceptability of risk and to identify key studies that are required for human health risk assessment and also opportunities for study waivers.


Asunto(s)
Protección de Cultivos , Exposición Profesional , Animales , Humanos , Medición de Riesgo
13.
Zootaxa ; 4966(2): 237244, 2021 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-34186619

RESUMEN

The pennatulacean genus Balticina has had a long and confusing taxonomic history, with serious nomenclatural problems that remain unresolved. Owing to disagreements about authorships and dates of publication, the names Pavonaria, Norticina and Halipteris have all been used as valid in place of Balticina, or else been regarded as its junior synonyms, even simultaneously. In this paper, after an extensive literature review, we determine the authorships and dates for all the taxa involved in accordance with the provisions of the International Code of Zoological Nomenclature and establish Balticina Gray, 1870 (=Halipteris) and Balticinidae Balss, 1910 (=Halipteridae) as the valid genus and family names, respectively, for this group of sea pens. We also propose the replacement name Rakollikeria for the preoccupied genus name Pavonaria Kölliker, 1870 (Balticinidae) (nec Schweigger, 1819 - Funiculinidae).


Asunto(s)
Antozoos/clasificación , Animales
14.
Zookeys ; 1019: 1-14, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33679169

RESUMEN

The recently described deep-sea pennatulacean genus Porcupinella was previously known only by the type species, Porcupinella profunda from the equatorial eastern Atlantic to the eastern North Atlantic Ocean. New data is provided on morphology, distribution, bathymetry, and related taxa. A second species is added here as well - a new species is described from the Tasman Sea in the southwestern Pacific. The new species, Porcupinella tasmanica, is distinguished from P. profunda by its distinctive hook-shaped growth form, laterally compressed dorsal keel, and differing regions that are occupied by siphonozooids. A key to the species of the deep-sea pennatulacean family Chunellidae is included based on comparative morphology.

15.
Pediatr Rheumatol Online J ; 19(1): 14, 2021 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-33593401

RESUMEN

BACKGROUND: Prompt diagnosis of juvenile idiopathic arthritis (JIA) is important to avoid long term complications. Elevated serum 14-3-3η levels improve the diagnostic sensitivity of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibody in adult rheumatoid arthritis (RA), and have been associated with more severe phenotype. We investigated the prevalence and clinical significance of serum 14-3-3η in different types of JIA. METHODS: JIA patients (n = 151) followed by the Pediatric Rheumatology Core at Children's Hospital of Los Angeles were categorized into 5 groups: polyarticular JIA RF+ (PJIA RF+; n = 39), PJIA RF- (n = 39), psoriatic arthritis (PsA; n = 19), enthesitis-related arthritis (ERA; n = 18), and oligoarticular JIA (OJIA [control group]; n = 36). RF, CCP antibody, and 14-3-3η were measured for all patients. 14-3-3η serum levels > 0.2 ng/mL were considered positive. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score-71 (JADAS-71). RESULTS: Elevated 14-3-3η levels were detected in 34/151 (23%) patients, and across all groups tested. Most patients with 14-3-3η had titers ≥4 times above the cutoff value. The majority (22, 65%) of 14-3-3η-positive patients were also positive for RF or CCP antibodies, 16 (47%) were positive for all 3, and 12 (35%) were single-positive for 14-3-3η. The highest prevalence of 14-3-3η was in PJIA RF+ patients (49%), followed by OJIA (22%). Positivity for 14-3-3η was not significantly associated with disease activity or age at diagnosis. CONCLUSION: Serum 14-3-3η can be detected in all forms of JIA tested but appears to be most common in PJIA RF+. 14-3-3η does not appear to correlate with disease activity in JIA.


Asunto(s)
Proteínas 14-3-3/sangre , Artritis Juvenil , Péptidos Cíclicos/inmunología , Factor Reumatoide/sangre , Artritis Juvenil/sangre , Artritis Juvenil/diagnóstico , Autoanticuerpos/sangre , Biomarcadores/sangre , Niño , Femenino , Humanos , Masculino , Gravedad del Paciente , Prevalencia , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Estados Unidos/epidemiología
16.
Domest Anim Endocrinol ; 73: 106539, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32917343
17.
Food Chem Toxicol ; 145: 111652, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32745573

RESUMEN

4-Methylimidazole (4-MeI) is a byproduct formed during the cooking of foods containing carbohydrates and amino acids, including the production of flavors and coloring substances, e.g., class III and IV caramel colors, used in many food products with extensive human exposure. Two-year rodent bioassays via oral exposure conducted by the National Toxicology Program reported evidence of carcinogenicity only in B6C3F1 mice (increased alveolar/bronchial neoplasms). In 2011, the International Agency for Research on Cancer classified 4-MeI as Group 2B, "possibly carcinogenic to humans". An expert panel was commissioned to assess the genotoxic potential of 4-MeI and the plausibility of a genotoxic mode of action in the formation of lung tumors in mice when exposed to high doses of 4-MeI. The panel defined and used a weight-of-evidence (WOE) approach that included thorough evaluation of studies assessing the genotoxic potential of 4-MeI. The panelists categorized each study, consisting of study weight, degree of technical performance, study reliability, and contribution to the overall WOE. Based on the reviewed studies' weighted contribution, the panel unanimously concluded that the WOE supports no clear evidence of in vivo genotoxicity of 4-MeI and no association for a genotoxic mode of action in the formation of mouse lung tumors.


Asunto(s)
Imidazoles/toxicidad , Neoplasias Pulmonares/epidemiología , Animales , Línea Celular , Humanos , Ratones , Pruebas de Mutagenicidad
18.
J Surg Case Rep ; 2020(6): rjaa163, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32665831

RESUMEN

Metastatic salivary gland tumors are rare clinical entities of the head and neck. Parotid gland carcinoma with distant metastases heralds a poor prognosis with a median survival of 4.3-7.3 months. The lungs, long bones, liver and brain are the most common sites of metastasis for parotid gland cancer, along with a few reported cases describing metastasis to the ileum, spleen and iliac crest. We present the first case to our knowledge of parotid adenocarcinoma metastasis to the breast.

19.
Crit Care Med ; 48(8): e648-e656, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32697505

RESUMEN

OBJECTIVES: Gestational age at birth is declining, probably because more deliveries are being induced. Gestational age is an important modifiable risk factor for neonatal mortality and morbidity. We aimed to investigate the association between gestational age and mortality in hospital for term-born neonates (≥ 37 wk') admitted to PICUs in Australia and New Zealand. DESIGN: Observational multicenter cohort study. SETTING: PICUs in Australia and New Zealand. PATIENTS: Term-born neonates (≥ 37 wk) admitted to PICUs. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS:: We studied 5,073 infants born with a gestational age greater than or equal to 37 weeks and were less than 28 days old when admitted to a PICU in Australia or New Zealand between 2007 and 2016. The association between gestational age and mortality was estimated using a multivariable logistic regression model, adjusting for age, sex, indigenous status, Pediatric Index of Mortality version 2, and site. The median gestational age was 39.1 weeks (interquartile range, 38.2-40 wk) and mortality in hospital was 6.6%. Risk of mortality declined log-linearly with gestational age. The adjusted analysis showed a 20% (95% CI, 11-28%) relative reduction in mortality for each extra week of gestation beyond 37 weeks. The effect of gestation was stronger among those who received extracorporeal life support: each extra week of gestation was associated with a 44% (95% CI, 25-57%) relative reduction in mortality. Longer gestation was also associated with reduced length of stay in hospital: each week increase in gestation, the average length of stay decreased by 4% (95% CI, 2-6%). CONCLUSIONS: Among neonates born at "term" who are admitted to a PICU, increasing gestational age at birth is associated with a substantial reduction in the risk of dying in hospital. The maturational influence on outcome was more strongly noted in the sickest neonates, such as those requiring extracorporeal life support. This information is important in view of the increasing proportion of planned births in both high- and low-/middle-income countries.


Asunto(s)
Enfermedad Crítica/mortalidad , Enfermedades del Recién Nacido/mortalidad , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Australia/epidemiología , Femenino , Edad Gestacional , Humanos , Recién Nacido , Masculino , Nueva Zelanda/epidemiología , Factores de Riesgo
20.
Theriogenology ; 148: 37-47, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32126394

RESUMEN

The objective of this study was to determine the effects of bovine nerve growth factor-ß (NGF) on pre-ovulatory follicle vascular area, LH release, ovulation, and luteal function when administered systemically to heifers. Post-pubertal Holstein heifers (n = 12) received an intravaginal progesterone-releasing device (CIDR) and GnRH agonist (100 µg IM). The CIDR was removed 5 d later, and heifers were given dinoprost (25 mg IM) at CIDR removal and 24 h later, followed by a second dose of GnRH agonist 48 h later. Heifers were randomly assigned to treatments using a cross-over design. For example, heifers assigned to NGF (250 µg reconstituted in 12 mL PBS IM) in replicate 1 were assigned to control (12 mL PBS IM) in replicate 2. Transrectal ultrasonography was performed before treatment and repeated every 4 h up to 32 h to determine the pre-ovulatory follicle diameter, vascular area, and ovulation. Serum samples were obtained to assess LH concentrations during the periovulatory period and every 2 d post-ovulation for measuring progesterone concentrations. A subset of heifers had luteal biopsies performed on days 9 (n = 6 per treatment) and 14 (n = 6 per treatment) post-ovulation to count luteal cell numbers and measure relative mRNA abundance for steroidogenic and angiogenic enzymes and LH receptor. Treatment with NGF increased pre-ovulatory follicle diameter (P = 0.02) and serum LH concentrations (P = 0.03) but did not affect time to ovulation (P = 0.42). Heifers treated with NGF had increased serum progesterone concentrations in the subsequent luteal phase (P = 0.03), but no change in vascular area of the follicle (P = 0.16) or CL (P = 0.20). Heifers treated with NGF had a greater number of small luteal cells (P < 0.01) and a tendency for increased LH receptor (LHR) mRNA abundance in the CL (P = 0.10). There was also increased steroidogenic acute regulatory protein (STAR; P = 0.05) and a tendency for increased cytochrome P450 family 11 (CYP11A1; P = 0.10) mRNA abundance in the CL of NGF-treated heifers. There was decreased prostaglandin E2 synthase (PGES; P = 0.03) and its receptor (PGER; P = 0.05) mRNA abundance and a tendency for decreased cytochrome P450 family 17 subfamily A member 1 (CYP17A1; P = 0.08) and hydroxysteroid 17-beta dehydrogenase (HSD17B; P = 0.06) mRNA abundance in the CL of NGF-treated heifers. Administration of NGF improved CL function in heifers potentially as a result of increased LH release.


Asunto(s)
Bovinos , Cuerpo Lúteo/efectos de los fármacos , Hormona Luteinizante/metabolismo , Factor de Crecimiento Nervioso/farmacología , Folículo Ovárico/efectos de los fármacos , Animales , Femenino
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