Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.552
Filtrar
1.
Toxicol Lett ; 397: 42-47, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38723915

RESUMO

Organophosphate pesticide poisoning challenges health care systems worldwide. Furthermore, nerve agents remain a continuous threat. The treatment options for organophosphate poisoning have virtually been unchanged for decades, relying on symptomatic treatment and the use of oximes to indirectly restore neuromuscular function. Hence, compounds targeting directly nicotinic acetylcholine receptors (nAChRs) might substantially improve treatment options. The current study investigated a series of bispyridinium analogues with a trimethylene or 2,2'-diethyloxy linker in a rat hemidiaphragm model, using indirect field stimulation. Methyl- and ethyl-substituted bispyridinium analogues restored neuromuscular function up to 37 ± 17% (MB419, a 3-methyl analogue) at a stimulation frequency of 20 Hz. The bispyridinium analogues with a 2- or 3-methyl group, or a 2- or 3-ethyl group, tended towards a higher restoration of neuromuscular function than those with a 4-methyl or 4-ethyl group, respectively. The current data can be used for future studies to optimize structure-based molecular modeling of compounds targeting the nAChR.

2.
Toxicology ; 503: 153741, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38311098

RESUMO

Organophosphate (OP) poisoning is currently treated with atropine, oximes and benzodiazepines. The nicotinic signs, i.e., respiratory impairment, can only be targeted indirectly via the use of oximes as reactivators of OP-inhibited acetylcholinesterase. Hence, compounds selectively targeting nicotinic acetylcholine receptors (nAChRs) might fundamentally improve current treatment options. The bispyridinium compound MB327 has previously shown some therapeutic effect against nerve agents in vitro and in vivo. Nevertheless, compound optimization was deemed necessary, due to limitations (e.g., toxicity and efficacy). The current study investigated a series of 4-tert-butyl bispyridinium compounds and of corresponding bispyridinium compounds without substituents in a rat diaphragm model using an indirect field stimulation technique. The length of the respective linker influenced the ability of the bispyridinium compounds to restore muscle function in rat hemidiaphragms. The current data show structure-activity relationships for a series of bispyridinium compounds and provide insight for future structure-based molecular modeling.


Assuntos
Reativadores da Colinesterase , Agentes Neurotóxicos , Intoxicação por Organofosfatos , Ratos , Animais , Oximas/farmacologia , Oximas/uso terapêutico , Agentes Neurotóxicos/toxicidade , Diafragma , Acetilcolinesterase/metabolismo , Compostos de Piridínio/farmacologia , Compostos de Piridínio/uso terapêutico , Relação Estrutura-Atividade , Intoxicação por Organofosfatos/tratamento farmacológico , Reativadores da Colinesterase/farmacologia , Inibidores da Colinesterase/farmacologia
3.
Braz. j. biol ; 842024.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469281

RESUMO

Abstract Endozoochory by waterbirds is particularly relevant to the dispersal of non-flying aquatic invertebrates. This ecological function exercised by birds has been demonstrated in different biogeographical regions, but there are no studies for the neotropical region. In this work, we identified propagules of invertebrates in faeces of 14 syntopic South American waterbird species representing six families, and hatched additional invertebrates from cultured faeces. We tested whether propagule abundance, species richness and composition varied among bird species, and between the cold and warm seasons. We found 164 invertebrate propagules in faecal samples from seven different waterbirds species, including eggs of the Temnocephalida and Notonectidae, statoblasts of bryozoans (Plumatella sp.) and ephippia of Cladocera. Ciliates (including Paramecium sp. and Litostomatea), nematodes and rotifers (Adineta sp. and Nottomatidae) hatched from cultured samples. Potential for endozoochory was confirmed for 12 of 14 waterbird species. Our statistical models suggest that richness and abundance of propagules are associated with bird species and not affected by seasonality. Dispersal by endozoochory is potentially important to a broad variety of invertebrates, being promoted by waterbirds with different ecological and morphological traits, which are likely to drive the dispersal of invertebrates in neotropical wetlands.


Resumo A endozoocoria promovida por aves aquáticas é particularmente relevante para a dispersão de invertebrados aquáticos não-voadores. Essa função ecológica exercida pelas aves tem sido demonstrada para diferentes regiões biogeográficas, porém, não existem estudos para a região neotropical. Neste trabalho nós identificamos propágulos de invertebrados encontrados em fezes de 14 espécies sintópicas de aves aquáticas da América do Sul, representando seis famílias de aves, e também invertebrados emergidos de amostras fecais cultivadas em laboratório. Testamos se a abundância, riqueza de espécies e composição de propágulos de invertebrados variavam entre as espécies de aves e entre estações. Nós encontramos 164 propágulos de invertebrados em amostras fecais de sete espécies de aves, incluindo ovos de Temnocephalida e Notonectidae, estatoblastos de briozoários (Plumatella sp.) e efípios de Cladocera. Ciliados (incluindo Paramecium sp. e Litostomatea), nematóides e rotíferos (Adineta sp. e Nottomatidae) eclodiram de amostras cultivadas. O potencial para endozoocoria foi confirmado para 12 das 14 espécies de aves aquáticas investigadas. Nossos modelos estatísticos sugerem que a riqueza e abundância de propágulos estão associadas às espécies de aves e não são afetadas pela sazonalidade. A dispersão por endozoocoria é importante para uma ampla variedade de invertebrados, sendo promovida por aves aquáticas com diferentes características ecológicas e morfológicas as quais provavelmente regulam a dispersão de invertebrados entre áreas úmidas neotropicais.

4.
Braz. j. biol ; 84: e250280, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355867

RESUMO

Abstract Endozoochory by waterbirds is particularly relevant to the dispersal of non-flying aquatic invertebrates. This ecological function exercised by birds has been demonstrated in different biogeographical regions, but there are no studies for the neotropical region. In this work, we identified propagules of invertebrates in faeces of 14 syntopic South American waterbird species representing six families, and hatched additional invertebrates from cultured faeces. We tested whether propagule abundance, species richness and composition varied among bird species, and between the cold and warm seasons. We found 164 invertebrate propagules in faecal samples from seven different waterbirds species, including eggs of the Temnocephalida and Notonectidae, statoblasts of bryozoans (Plumatella sp.) and ephippia of Cladocera. Ciliates (including Paramecium sp. and Litostomatea), nematodes and rotifers (Adineta sp. and Nottomatidae) hatched from cultured samples. Potential for endozoochory was confirmed for 12 of 14 waterbird species. Our statistical models suggest that richness and abundance of propagules are associated with bird species and not affected by seasonality. Dispersal by endozoochory is potentially important to a broad variety of invertebrates, being promoted by waterbirds with different ecological and morphological traits, which are likely to drive the dispersal of invertebrates in neotropical wetlands.


Resumo A endozoocoria promovida por aves aquáticas é particularmente relevante para a dispersão de invertebrados aquáticos não-voadores. Essa função ecológica exercida pelas aves tem sido demonstrada para diferentes regiões biogeográficas, porém, não existem estudos para a região neotropical. Neste trabalho nós identificamos propágulos de invertebrados encontrados em fezes de 14 espécies sintópicas de aves aquáticas da América do Sul, representando seis famílias de aves, e também invertebrados emergidos de amostras fecais cultivadas em laboratório. Testamos se a abundância, riqueza de espécies e composição de propágulos de invertebrados variavam entre as espécies de aves e entre estações. Nós encontramos 164 propágulos de invertebrados em amostras fecais de sete espécies de aves, incluindo ovos de Temnocephalida e Notonectidae, estatoblastos de briozoários (Plumatella sp.) e efípios de Cladocera. Ciliados (incluindo Paramecium sp. e Litostomatea), nematóides e rotíferos (Adineta sp. e Nottomatidae) eclodiram de amostras cultivadas. O potencial para endozoocoria foi confirmado para 12 das 14 espécies de aves aquáticas investigadas. Nossos modelos estatísticos sugerem que a riqueza e abundância de propágulos estão associadas às espécies de aves e não são afetadas pela sazonalidade. A dispersão por endozoocoria é importante para uma ampla variedade de invertebrados, sendo promovida por aves aquáticas com diferentes características ecológicas e morfológicas as quais provavelmente regulam a dispersão de invertebrados entre áreas úmidas neotropicais.


Assuntos
Humanos , Animais , Áreas Alagadas , Invertebrados , Estações do Ano , Aves
6.
Nat Commun ; 14(1): 6197, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794061

RESUMO

The layered-ruthenate family of materials possess an intricate interplay of structural, electronic and magnetic degrees of freedom that yields a plethora of delicately balanced ground states. This is exemplified by Ca3Ru2O7, which hosts a coupled transition in which the lattice parameters jump, the Fermi surface partially gaps and the spins undergo a 90∘ in-plane reorientation. Here, we show how the transition is driven by a lattice strain that tunes the electronic bandwidth. We apply uniaxial stress to single crystals of Ca3Ru2O7, using neutron and resonant x-ray scattering to simultaneously probe the structural and magnetic responses. These measurements demonstrate that the transition can be driven by externally induced strain, stimulating the development of a theoretical model in which an internal strain is generated self-consistently to lower the electronic energy. We understand the strain to act by modifying tilts and rotations of the RuO6 octahedra, which directly influences the nearest-neighbour hopping. Our results offer a blueprint for uncovering the driving force behind coupled phase transitions, as well as a route to controlling them.

7.
Dalton Trans ; 52(37): 13110-13118, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37675851

RESUMO

Niobium based anodes are gaining increasing popularity for application in high-power lithium-ion batteries, due to their high theoretical capacities, inherent safety at high current densities, and long-term stability. Here, we report the discovery and characterisation of a new Wadsley Roth niobate system, Nb7Ti1.5Mo1.5O25, showing that it is isostructural with known systems: Nb9PO25 and Nb9VO25. To evaluate the material's electrochemical performance, including performance at high current densities (for potential high power applications), and long-term stability, Li half-coin cells were prepared. The material showed an initial capacity of 268(9) mA h g-1 at 0.01 A g-1 (voltage range of 2.5-1.0 V). However, in subsequent cycles, some of this initial capacity is lost, which is attributed to Li trapping associated with the presence of reducible MoO4 units, similar to the situation observed for isostructural Nb9VO25. After this initial irreversible capacity loss, the material showed good performance at high current density rates, such that at 2 A g-1 and 4 A g-1 respective capacities of 132(10) mA h g-1 and 115(14) mA g-1 were delivered. Moreover, the material showed respectable capacity retention (97%) after being cycled for 100 cycles at 0.2 A g-1. In order to identify the different Nb, Ti, Mo redox couples involved in this system, a Ta analogue was also synthesized (Ta7Ti1.5Mo1.5O25) and the electrochemical performance for this phase is also reported. This phase shows a lower initial capacity at 0.01 A g-1 (140(3) mA h g-1) than the Nb analogue in the same voltage range, which can be increased (225 mA h g-1) if a lower cutoff voltage (0.5 V) is applied. The capacity retention for this Ta system after 100 cycles at 0.2 A g-1 is similar to the Nb analogue (97%). Further work has explored whether the Nb-Ti-Mo contents could be varied, and these results showed that single phase Nb10-2xTixMoxO25 samples could be prepared for 1.5 ≤ x ≤ 1.75, and electrochemical testing results for the x = 1.75 endmember are also reported. Overall, this research highlights the synthesis and electrochemical characterisation of two new Wadsley Roth phases, and further highlights the challenges associated with the presence of reducible cations in tetrahedral sites in such structures with respect to minimising initial irreversible capacity loss.

8.
Blood Cells Mol Dis ; 102: 102762, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37276838

RESUMO

Fanconi anaemia (FA) is a rare autosomal recessive condition resulting in changes in the FANC gene family. This report describes a case of Fanconi anaemia in a family with complex biallelic variants. The patient is a 32-year-old female diagnosed with FA on cascade testing during childhood with chromosome breakage studies. On examination she had a fixed deformity of the right thumb and the proximal interphalangeal joint was immobile. Her brother shared this radial abnormality and had FA, requiring a bone marrow transplant. She presented in adulthood seeking further BRCA advice and had next generation sequencing that showed three variants in the FANCA gene. One allele a known pathogenic change, the other had two sequence variants in tandem that have been reported as variants of uncertain significance. There is one other unrelated case of these two variants occurring together in cis, resulting in Fanconi anaemia. This case is an interesting example of three variants in the FANCA gene, one allele with a pathogenic deletion and the other with a single complex allele made up of two missense variants of uncertain significance, likely manifesting with FA. It highlights the utility of different genetic technologies in the interpretation of next generation sequencing.


Assuntos
Anemia de Fanconi , Humanos , Masculino , Feminino , Adulto , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/genética , Anemia de Fanconi/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Genômica , Mutação de Sentido Incorreto , Mutação
9.
J R Soc Med ; 116(10): 331-342, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37343667

RESUMO

OBJECTIVES: To audit national drug registers (NDRs) in Kenya, United Republic of Tanzania and Uganda with respect to national Essential Medicine Lists (EMLs) and to conduct an analysis of highly registered products including a sub-analysis of highly registered antimicrobial products. DESIGN: Retrospective analysis of registration of essential medicines and medicinal products on NDRs as of February 2018. SETTING: Not applicable. PARTICIPANTS: None. MAIN OUTCOME MEASURES: Registration status of essential medicines by country, essential medicine status of registered products by country and medicines with more than 50 registrations across all three countries. RESULTS: A high proportion of essential medicines are not registered: Kenya 28% (175/632), United Republic of Tanzania 50% (400/797) and Uganda 40% (266/663). Of registered products on the NDRs, more than half are not essential: Kenya 71% (4350/6151), United Republic of Tanzania 64% (2278/3590) and Uganda 58% (2268/3896). When the three NDRs were combined, there were 42 medicines with over 50 registered products, accounting for 30% (4153/13637) of products, many of which were non-essential. CONCLUSIONS: Non-registration of essential medicines is a barrier to availability. Over-registration of medicines, particularly non-essential medicines, diverts regulatory resources towards registering non-priority and, sometimes, clinically sub-optimal medicines. The East African Community Medicines Registration Harmonization Project has the potential to improve access to key medicines if registration of essential medicines is prioritised and registration of non-essential medicines is restricted.


Assuntos
Medicamentos Essenciais , Humanos , Quênia , Uganda , Tanzânia , Estudos Retrospectivos
10.
Rev Sci Tech ; 42: 52-64, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37232319

RESUMO

Monitoring antimicrobial use (AMU) and antimicrobial resistance (AMR) on farms is recognised as an important component of antimicrobial stewardship, yet the process can be resource intensive. This paper describes a subset of findings from the first year of a collaboration across government, academia and a private sector veterinary practice focused on swine production in the Midwestern United States. The work is supported by participating farmers and the greater swine industry. Twice-annual collection of samples from pigs along with AMU monitoring occurred on 138 swine farms. Detection and resistance of Escherichia coli from pig tissues was assessed, and associations between AMU and AMR were evaluated. This paper describes the methods utilised and the first-year E. coli-related results from this project. Higher minimum inhibitory concentrations (MIC) for enrofloxacin and danofloxacin in E. coli from swine tissues were associated with the purchase of fluoroquinolones. There were no other significant associations between MIC and AMU combinations in E. coli isolated from pig tissues. This project represents one of the first attempts to monitor AMU as well as AMR in E. coli in a large-scale commercial swine system in the United States of America.


Alors même que la surveillance exercée sur l'utilisation des agents antimicrobiens (UAM) et sur la résistance aux agents antimicrobiens (RAM) dans les élevages est une composante majeure reconnue de la gestion des antimicrobiens, le processus en lui-même exige une mobilisation intensive de ressources. Les auteurs décrivent un sous-ensemble de résultats obtenus au cours de la première année d'une collaboration entre les pouvoirs publics, les universités et une clinique vétérinaire privée, axée sur la production porcine dans le Midwest des états-Unis d'Amérique. Ce travail est soutenu par les éleveurs participants et par le secteur porcin au sens large. Une collecte d'échantillons porcins a été effectuée deux fois par an, parallèlement à la surveillance de l'UAM dans 138 élevages. Il a été procédé à une recherche des Escherichia coli présents dans les tissus porcins prélevés puis à la détermination de la résistance aux antimicrobiens chez les microorganismes détectés ; les corrélations éventuelles entre l'UAM et la RAM ont ensuite été évaluées. Les auteurs décrivent les méthodes utilisées dans la cadre de ce projet ainsi que les résultats en lien avec les E. coli obtenus au cours de la première année. Une corrélation a été constatée entre l'augmentation des concentrations minimales inhibitrices (CMI) recueillies pour l'enrofloxacine et la danofloxacine vis-à-vis d'E. coli dans les tissus porcins analysés, d'une part, et l'achat de fluoroquinolones, d'autre part. Aucune autre corrélation significative n'a été décelée entre les CMI recueillies et les profils d'UAM concernant les E. coli isolés à partir des tissus porcins. Ce projet représente l'une des premières tentatives conduites aux états-Unis d'Amérique pour surveiller parallèlement l'UAM et la RAM chez les E. coli dans un système commercial de production porcine à grande échelle.


Aunque se tiene por sabido que la vigilancia en las explotaciones del uso de agentes antimicrobianos (UAM) y de la resistencia a los antimicrobianos (RAM) es un importante componente de la gestión de estos fármacos, no es menos cierto que el proceso puede consumir cuantiosos recursos. Los autores exponen un ubconjunto de observaciones realizadas durante el primer año de un proyecto de colaboración entre la administración pública, el mundo universitario y una clínica veterinaria privada que tenía por objeto de estudio la producción porcina en la zona del medio oeste de los Estados Unidos de América. Respaldaban el proyecto los productores que participaban en él y el sector de la industria porcina en general. Dos veces al año se obtuvieron muestras en 138 explotaciones porcinas, en las que también se seguía de cerca el UAM. Tras realizar pruebas de detección de Escherichia coli en tejidos porcinos y analizar la resistencia de esos microorganismos a antimicrobianos, se buscaron correlaciones entre el uso de estos fármacos y la presencia de eventuales resistencias. Los autores describen los métodos empleados y los resultados obtenidos el primer año del proyecto en relación con E. coli. Se observó una correlación entre la compra de fluoroquinolonas y el aumento de la concentración inhibitoria mínima (MIC) de enrofloxacina y de danofloxacina en los E. coli analizados. No se constató ninguna otra asociación significativa entre las MIC y el uso de diferentes antimicrobianos en los E. coli aislados a partir de tejido porcino. Este proyecto constituye una de las primeras tentativas de hacer seguimiento y balance del uso de agentes antimicrobianos y de la resistencia de E. coli a estos fármacos en el sistema de producción porcina industrial de los Estados Unidos de América.


Assuntos
Antibacterianos , Anti-Infecciosos , Suínos , Animais , Estados Unidos , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Escherichia coli , Farmacorresistência Bacteriana , Anti-Infecciosos/farmacologia , Fazendeiros
11.
Artigo em Inglês | MEDLINE | ID: mdl-37169608
12.
Sci Rep ; 13(1): 8866, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37258551

RESUMO

We introduce a Langevin unravelling of the density matrix evolution of an open quantum system over matrix product states, which we term the time-dependent variational principle-Langevin equation. This allows the study of entanglement dynamics as a function of both temperature and coupling to the environment. As the strength of coupling to and temperature of the environment is increased, we find a transition where the entanglement of the individual trajectories saturates, permitting a classical simulation of the system for all times. This is the Hamiltonian open system counterpart of the saturation in entanglement found in random circuits with projective or weak measurements. If a system is open, there is a limit to the advantage in simulating its behaviour on a quantum computer, even when that evolution harbours important quantum effects. Moreover, if a quantum simulator is in this phase, it cannot simulate with quantum advantage.

13.
PLoS One ; 18(4): e0284786, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37083685

RESUMO

Organophosphate intoxication via acetylcholinesterase inhibition executes neurotoxicity via hyper stimulation of acetylcholine receptors. Here, we use the organophosphate paraoxon-ethyl to treat C. elegans and use its impact on pharyngeal pumping as a bio-assay to model poisoning through these neurotoxins. This assay provides a tractable measure of acetylcholine receptor mediated contraction of body wall muscle. Investigation of the time dependence of organophosphate treatment and the genetic determinants of the drug-induced inhibition of pumping highlight mitigating modulation of the effects of paraoxon-ethyl. We identified mutants that reduce acetylcholine receptor function protect against the consequence of intoxication by organophosphates. Data suggests that reorganization of cholinergic signalling is associated with organophosphate poisoning. This reinforces the under investigated potential of using therapeutic approaches which target a modulation of nicotinic acetylcholine receptor function to treat the poisoning effects of this important class of neurotoxins.


Assuntos
Intoxicação por Organofosfatos , Receptores Nicotínicos , Animais , Intoxicação por Organofosfatos/tratamento farmacológico , Paraoxon/uso terapêutico , Paraoxon/toxicidade , Inibidores da Colinesterase/uso terapêutico , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Acetilcolinesterase/metabolismo , Receptores Nicotínicos/genética , Neurotoxinas , Organofosfatos/toxicidade , Organofosfatos/uso terapêutico
14.
Toxins (Basel) ; 15(4)2023 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-37104219

RESUMO

The pathogenesis of ricin toxicity following inhalation has been investigated in many animal models, including the non-human primate (predominantly the rhesus macaque), pig, rabbit and rodent. The toxicity and associated pathology described in animal models are broadly similar, but variation appears to exist. This paper reviews the published literature and some of our own unpublished data and describes some of the possible reasons for this variation. Methodological variation is evident, including method of exposure, breathing parameters during exposure, aerosol characteristics, sampling protocols, ricin cultivar, purity and challenge dose and study duration. The model species and strain used represent other significant sources of variation, including differences in macro- and microscopic anatomy, cell biology and function, and immunology. Chronic pathology of ricin toxicity by inhalation, associated with sublethal challenge or lethal challenge and treatment with medical countermeasures, has received less attention in the literature. Fibrosis may follow acute lung injury in survivors. There are advantages and disadvantages to the different models of pulmonary fibrosis. To understand their potential clinical significance, these factors need to be considered when choosing a model for chronic ricin toxicity by inhalation, including species and strain susceptibility to fibrosis, time it takes for fibrosis to develop, the nature of the fibrosis (e.g., self-limiting, progressive, persistent or resolving) and ensuring that the analysis truly represents fibrosis. Understanding the variables and comparative aspects of acute and chronic ricin toxicity by inhalation is important to enable meaningful comparison of results from different studies, and for the investigation of medical countermeasures.


Assuntos
Ricina , Animais , Coelhos , Suínos , Ricina/toxicidade , Pulmão/patologia , Macaca mulatta , Administração por Inalação , Fibrose
15.
Life Sci ; 312: 121252, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36460096

RESUMO

Chlorine (Cl2) gas is a toxic industrial chemical (TIC) that poses a hazard to human health following accidental and/or intentional (e.g. terrorist) release. By using a murine model of sub-lethal Cl2 exposure we have examined the airway hyper responsiveness, cellular infiltrates, transcriptomic and proteomic responses of the lung. In the "crisis" phase at 2 h and 6 h there is a significant decreases in leukocytes within bronchoalveolar lavage fluid accompanied by an upregulation within the proteome of immune pathways ultimately resulting in neutrophil influx at 24 h. A flip towards "repair" in the transcriptome and proteome occurs at 24 h, neutrophil influx and an associated drop in the lung function persisting until 14 d post-exposure and subsequent "recovery" after 28 days. Collectively, this research provides new insights into the mechanisms of damage, early global responses and processes of repair induced in the lung following the inhalation of Cl2.


Assuntos
Cloro , Proteoma , Camundongos , Humanos , Animais , Cloro/toxicidade , Proteômica , Pulmão , Líquido da Lavagem Broncoalveolar
16.
Eur J Pediatr ; 182(1): 31-40, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36374302

RESUMO

The Irish Traveller population are an endogamous, traditionally nomadic, Irish population. Irish Travellers practice consanguinity in the majority of marriages, thus resulting in a higher rate of rare autosomal recessive conditions within the population due to homozygous variants. Herein, we outline the clinical phenotypes associated with metabolic conditions seen in this population presenting in the neonatal period, infancy and childhood. Although Irish Travellers are traditionally based in Ireland and the UK, there are populations also living in mainland Europe and the USA. While there is generally an understanding amongst Irish paediatricians of the recessive conditions seen with this population in Ireland, they may be less commonly encountered abroad. It is important to consider a non-genetic aetiology alongside any consideration for a metabolic disorder. CONCLUSION: This paper acts as a comprehensive review of the metabolic conditions seen and provides a guide for the investigation of an Irish Traveller child with a suspected metabolic condition. WHAT IS KNOWN: • The Irish Traveller population are an endogenous population. • There are higher rates of inherited metabolic conditions in this population compared to the general population in Ireland. WHAT IS NEW: • This paper is a comprehensive review of all known inherited metabolic conditions encountered in the Irish Traveller population.


Assuntos
Viagem , Humanos , Europa (Continente) , Irlanda/epidemiologia
17.
Arch Dermatol Res ; 315(3): 633-636, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36104631

RESUMO

The lower limb is a common site for melanoma in women, but the reason for this is not fully understood. To investigate this phenomenon in more detail, we assessed the specific subsites of primary melanoma occurring on the lower limbs of females compared with males across age groups. In a records-based study at an oncology hospital in north-west of England, among an unselected sample of patients with primary invasive melanoma treated between 2002-2015, information was collected on patient age at diagnosis, sex, and co-morbidities, and the tumor thickness and anatomical subsite (thigh, lower leg, foot for lower limb). Of a total sample of 1,522 patients, 316 (227, 72% female) had lower limb melanoma. The most common subsite was lower leg (142 cases with F:M ratio =3.74), followed by thigh (55 cases with F:M = 1.83) and feet (30 cases with F:M = 1.15). At ages <40 years the odds of thigh to foot melanoma was 20 times higher in females than in males (OR 20.0, 95% CI 2.6-152.6) and 7.5 times higher on the lower limb (OR 7.5, 95% CI 1.1-49.2). For ages 40+ years, the odds of females developing thigh melanoma compared to foot melanoma was similar in males versus females (OR 0.8), while the corresponding odds of lower leg melanoma in females versus males remained significantly increased at ages 40-59 and 60+ (OR 4.2 and 2.8 respectively). Our study demonstrates the female predilection for lower limb melanoma persists over most but not all subsites.However, there is heterogeneity in the female to male occurence of lower limb melanoma across subsites and at different ages, which may be linked to relative influence of genetic and environmental risk factors.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Feminino , Masculino , Adulto , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Melanoma/epidemiologia , Melanoma/patologia , Extremidade Inferior/patologia
18.
Semin Neurol ; 42(4): 404-405, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-36323297
19.
Nat Commun ; 13(1): 6620, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333309

RESUMO

As we approach the era of quantum advantage, when quantum computers (QCs) can outperform any classical computer on particular tasks, there remains the difficult challenge of how to validate their performance. While algorithmic success can be easily verified in some instances such as number factoring or oracular algorithms, these approaches only provide pass/fail information of executing specific tasks for a single QC. On the other hand, a comparison between different QCs preparing nominally the same arbitrary circuit provides an insight for generic validation: a quantum computation is only as valid as the agreement between the results produced on different QCs. Such an approach is also at the heart of evaluating metrological standards such as disparate atomic clocks. In this paper, we report a cross-platform QC comparison using randomized and correlated measurements that results in a wealth of information on the QC systems. We execute several quantum circuits on widely different physical QC platforms and analyze the cross-platform state fidelities.

20.
Nat Commun ; 13(1): 5977, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36216839

RESUMO

The phenomena of quantum criticality underlie many novel collective phenomena found in condensed matter systems. They present a challenge for classical and quantum simulation, in part because of diverging correlation lengths and consequently strong finite-size effects. Tensor network techniques that work directly in the thermodynamic limit can negotiate some of these difficulties. Here, we optimise a translationally invariant, sequential quantum circuit on a superconducting quantum device to simulate the groundstate of the quantum Ising model through its quantum critical point. We further demonstrate how the dynamical quantum critical point found in quenches of this model across its quantum critical point can be simulated. Our approach avoids finite-size scaling effects by using sequential quantum circuits inspired by infinite matrix product states. We provide efficient circuits and a variety of error mitigation strategies to implement, optimise and time-evolve these states.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...