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1.
Proc Biol Sci ; 291(2031): rspb20241086, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39288799

RESUMO

Climate change is driving both higher mean temperatures and a greater likelihood of heatwaves, which are becoming longer and more intense. Previous work has looked at these two types of thermal stressors in isolation, focusing on the effects of either a small, long-term increase in temperature or a large, short-term increase in temperature. Yet, a fundamental gap in our understanding is the combined effect of chronic and acute thermal stressors and, in particular, its impact on vital processes such as reproduction. Here, we investigated the independent and interactive effects of higher constant temperatures and short-term heatwave events on reproductive success and offspring fitness in an insect study system, the burying beetle Nicrophorus vespilloides. We found a substantial reduction in key fitness traits (fecundity, hatching success and offspring size) after exposure to both a heatwave and higher constant temperatures, but not after exposure to only one of these thermal stressors. This indicates that the effects of chronic and acute thermal stressors are amplified when they act in combination, as is very likely to occur in natural populations. Our findings, therefore, suggest that, by not considering the potential multiplicative effects of different types of thermal stressors, we may be underestimating the effects of climate change on animal fertility.


Assuntos
Mudança Climática , Besouros , Fertilidade , Animais , Besouros/fisiologia , Temperatura Alta , Reprodução , Feminino , Masculino , Estresse Fisiológico
2.
Pediatr Allergy Immunol ; 32(8): 1756-1763, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34152649

RESUMO

BACKGROUND: Internationally, the COVID-19 pandemic severely curtailed access to hospital facilities for those awaiting elective/semi-elective procedures. For allergic children in Ireland, already waiting up to 4 years for an elective oral food challenge (OFC), the restrictions signified indefinite delay. At the time of the initiative, there were approx 900 children on the Children's Health Ireland (CHI) waiting list. In July 2020, a project was facilitated by short-term (6 weeks) access to an empty COVID stepdown facility built, in a hotel conference centre, commandeered by the Health Service Executive (HSE), Ireland. The aim of this study was to achieve the rapid roll-out of an offsite OFC service, delivering high throughput of long waiting patients, while aligning with existing hospital policies and quality standards, international allergy guidelines and national social distancing standards. METHODS: The working group engaged key stakeholders to rapidly develop an offsite OFC facility. Consultant paediatric allergists, consultant paediatricians, trainees and allergy clinical nurse specialists were seconded from other duties. The facility was already equipped with hospital beds, bedside monitors (BP, pulse and oxygen saturation) and bedside oxygen. All medication and supplies had to be brought from the base hospital. Daily onsite consultant anaesthetic cover was resourced and a resuscitation room equipped. Standardized food challenge protocols were created. Access to the onsite hotel chef facilitated food preparation. A risk register was established. RESULTS: After 6 weeks of planning, the remote centre became operational on 7/9/2020, with the capacity of 27 OFC/day. 474 challenges were commenced: 465 (98%) were completed and 9 (2%) were inconclusive. 135 (29%) OFCs were positive, with 25 (5%) causing anaphylaxis. No child required advanced airway intervention. 8 children were transferred to the base hospital. The CHI allergy waiting list was reduced by almost 60% in only 24 days. CONCLUSIONS: Oral food challenges remain a vital tool in the care of allergic children, with their cost saving and quality-of-life benefits negatively affected by a delay in their delivery. This project has shown it is possible to have huge impacts on a waiting list efficiently, effectively and safely with good planning and staff buy-in-even in a pandemic. Adoption of new, flexible and efficient models of service delivery will be important for healthcare delivery in the post-COVID-19 era.


Assuntos
COVID-19 , Pandemias , Alérgenos , Alergistas , Criança , Humanos , SARS-CoV-2
3.
Pediatr Dev Pathol ; 22(4): 340-343, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30683018

RESUMO

A rare complication of umbilical venous catheter (UVC) insertion is the extravasation of the infusate into the peritoneal cavity. We report 3 cases of abdominal extravasation of parenteral nutrition (PN) fluid via UVCs. Two of these cases presented as "acute abdomen" which were assumed to be necrotizing enterocolitis clinically; however, during postmortem, PN ascites and liver necrosis were found. A further case is described in an infant with congenital diaphragmatic hernia. While we were unable to ascertain direct vessel perforation by the catheter in any of these cases, based on pathological and histological examination, the proposed mechanism of PN fluid extravasation is leakage through microinjuries of liver vessel walls and necrotic parenchyma. PN extravasation should be considered as a differential diagnosis of acute abdomen when PN is infused via an UVC presumably as PN may have a direct irritant effect on the peritoneum.


Assuntos
Abdome Agudo/etiologia , Ascite/etiologia , Cateteres de Demora/efeitos adversos , Extravasamento de Materiais Terapêuticos e Diagnósticos/complicações , Nutrição Parenteral Total/efeitos adversos , Abdome Agudo/diagnóstico , Abdome Agudo/fisiopatologia , Ascite/diagnóstico , Ascite/fisiopatologia , Extravasamento de Materiais Terapêuticos e Diagnósticos/diagnóstico , Extravasamento de Materiais Terapêuticos e Diagnósticos/fisiopatologia , Feminino , Humanos , Recém-Nascido , Gravidez , Veias Umbilicais/patologia , Veias Umbilicais/fisiologia
4.
J Interprof Care ; 30(5): 553-8, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27351897

RESUMO

Spontaneous learning is integral to definitions of interprofessional learning (IPL) because it has been suggested that spontaneous learning can be deeply connected with the work that people do in collaboration with colleagues via their professional networks. However, its nature and the processes involved are not well understood. Goffman's theory of impression management offers a useful theoretical framework to consider the way in which interaction in the workplace connects to spontaneous learning. This article explores the current literature to investigate the usefulness of this framework to better understand and identify spontaneous learning in the workplace. Aspects such as the connections between spontaneous learning occurring in formal and informal work activities, the spaces in which it occurs, and the influence of professional networking are considered. It is proposed that research directed to developing a better understanding of the nature of spontaneous learning in IPL will assist in connecting this learning to formal IPL curricula, enhancing IPL and patient outcomes.


Assuntos
Serviço Hospitalar de Emergência , Comunicação Interdisciplinar , Relações Interprofissionais , Teoria Psicológica , Humanos , Aprendizagem
5.
Blood ; 122(24): 3908-17, 2013 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-24021668

RESUMO

Transient abnormal myelopoiesis (TAM), a preleukemic disorder unique to neonates with Down syndrome (DS), may transform to childhood acute myeloid leukemia (ML-DS). Acquired GATA1 mutations are present in both TAM and ML-DS. Current definitions of TAM specify neither the percentage of blasts nor the role of GATA1 mutation analysis. To define TAM, we prospectively analyzed clinical findings, blood counts and smears, and GATA1 mutation status in 200 DS neonates. All DS neonates had multiple blood count and smear abnormalities. Surprisingly, 195 of 200 (97.5%) had circulating blasts. GATA1 mutations were detected by Sanger sequencing/denaturing high performance liquid chromatography (Ss/DHPLC) in 17 of 200 (8.5%), all with blasts >10%. Furthermore low-abundance GATA1 mutant clones were detected by targeted next-generation resequencing (NGS) in 18 of 88 (20.4%; sensitivity ∼0.3%) DS neonates without Ss/DHPLC-detectable GATA1 mutations. No clinical or hematologic features distinguished these 18 neonates. We suggest the term "silent TAM" for neonates with DS with GATA1 mutations detectable only by NGS. To identify all babies at risk of ML-DS, we suggest GATA1 mutation and blood count and smear analyses should be performed in DS neonates. Ss/DPHLC can be used for initial screening, but where GATA1 mutations are undetectable by Ss/DHPLC, NGS-based methods can identify neonates with small GATA1 mutant clones.


Assuntos
Células Clonais/metabolismo , Síndrome de Down/genética , Mutação , Doença Aguda , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Cromatografia Líquida de Alta Pressão/métodos , Células Clonais/patologia , Análise Mutacional de DNA/métodos , Síndrome de Down/sangue , Fator de Transcrição GATA1 , Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Recém-Nascido , Leucemia Mieloide/sangue , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/genética , Mielopoese/genética , Triagem Neonatal/métodos , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Pré-Leucemia/sangue , Pré-Leucemia/diagnóstico , Pré-Leucemia/genética , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade
6.
JDS Commun ; 5(5): 452-456, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39310844

RESUMO

There is currently societal interest and concern for dairy cow welfare. It has been suggested that boredom poses a welfare issue for dairy cows, particularly when presented with extended disposable time in housed environments that lack stimuli. Farm animals experience a multitude of affective states, which has created a need for positive experiences to be included in welfare management. Environmental enrichment can reduce boredom and facilitate positive experiences; however, the research in cows is limited. To assess the behavioral impact of a simple enrichment on commercially housed dairy cows, we provided 24-h access to a novel object, for 3 wk, for 2 separate groups of cows. Two boredom-associated behaviors significantly decreased when the object was present compared with when it was not present: "idling" behavior and unsuccessful robotic milking attempts ("refusals"). In addition, there was a significant increase in the occurrence of self-grooming during treatment weeks, when the novel object was present. These results suggest that idling and refusals may be behavioral indicators of boredom in dairy cows.

7.
Front Vet Sci ; 10: 1099170, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37008348

RESUMO

In addition to the reduction of suboptimal welfare, there is now a need to provide farmed animals with positive opportunities to provide confidence that they have experienced a life worth living. Diversification of the environment through environmental enrichment strategies is one suggested avenue for providing animals with opportunities for positive experiences. The provision of more stimulating environmental conditions has been widely implemented in other animal production industries, based on evidenced welfare benefits. However, the implementation of enrichment on dairy farms is limited. In addition to this, the relationship between enrichment and dairy cows' affective states is an under-researched area. One specific welfare benefit of enrichment strategies which has been observed in a number of species, is increased affective wellbeing. This study investigated whether the provision of different forms of environmental enrichment resources would impact the affective states of housed dairy cows. This was measured by Qualitative Behavioural Assessment, currently a promising positive welfare indicator. Two groups of cows experienced three treatment periods; (i) access to an indoor novel object, (ii) access to an outdoor concrete yard and (iii) simultaneous access to both resources. Principal component analysis was used to analyse qualitative behavioural assessment scores, which yielded two principal components. The first principal component was most positively associated with the terms "content/relaxed/positively occupied" and had the most negative associations with the terms 'fearful/bored'. A second principal component was most positively associated with the terms "lively/inquisitive/playful" and was most negatively associated with the terms "apathetic/bored". Treatment period had a significant effect on both principal components, with cows being assessed as more content, relaxed and positively occupied and less fearful and bored, during periods of access to additional environmental resources. Similarly, cows were scored as livelier, more inquisitive and less bored and apathetic, during treatment periods compared to standard housing conditions. Concurrent with research in other species, these results suggest that the provision of additional environmental resources facilitates positive experiences and therefore enhanced affective states for housed dairy cows.

8.
Mol Autism ; 14(1): 10, 2023 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-36871073

RESUMO

Autism was formally recognized by the medical community in the first half of the twentieth century. Almost 100 years later, a small but growing literature has reported sex differences in the behavioral expression of autism. Recent research has also begun to explore the internal experiences of individuals with autism, including social and emotional insight. The current study examines sex differences in language-based markers of social and emotional insight in girls and boys with autism and non-autistic peers during semi-structured clinical interviews. Sixty-four participants aged 5 to 17 years were individually matched on chronological age and full-scale IQ to form four groups: autistic girls, autistic boys, non-autistic girls, and non-autistic boys. Transcribed interviews were scored using four scales that index aspects of social and emotional insight. Results revealed the main effects of diagnosis, such that youth with autism exhibited lower insight than non-autistic youth on scales indexing social cognition and object relations, emotional investment, and social causality. With regards to sex differences, across diagnoses, girls were rated higher than boys on the social cognition and object relations, emotional investment, and social causality scales. Examined within each diagnosis separately, clear sex differences emerged: both autistic and non-autistic girls demonstrated better social cognition and understanding of social causality than boys in their respective diagnostic groups. No within-diagnosis sex differences were found on the emotional insight scales, however. These results suggest that relatively enhanced social cognition and understanding of social causality in girls may be a population-level sex difference that is preserved in autism, despite the core social challenges that characterize this condition. The current findings reveal critical new information about insight into social and emotional thinking and relationships in autistic girls versus boys that have important implications for improving identification and designing effective interventions.


Assuntos
Transtorno Autístico , Caracteres Sexuais , Humanos , Feminino , Adolescente , Masculino , Emoções , Idioma , Grupo Associado
9.
ACG Case Rep J ; 10(4): e01006, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37091202

RESUMO

Postinfantile giant cell hepatitis (PIGCH), also known as syncytial giant cell hepatitis, continues to be a poorly defined and rare disease presentation in the adult population. Although a common finding in neonates, there is limited literature on the disease process, causes, and treatment success of PIGCH in adults. A strong association between autoimmune disorders and PIGCH, considerably so in the case of autoimmune hepatitis, has been established. However, there have been limited to no reports of PIGCH secondary to rheumatoid arthritis. Our clinical case aims to bring forth a vignette of PIGCH to spotlight this ill-defined disease in the adult population and highlight some of the proposed causes, treatments, and laboratory markers.

10.
Mol Autism ; 14(1): 13, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024960

RESUMO

BACKGROUND: Autistic girls are underdiagnosed compared to autistic boys, even when they experience similar clinical impact. Research suggests that girls present with distinct symptom profiles across a variety of domains, such as language, which may contribute to their underdiagnosis. In this study, we examine sex differences in the temporal dynamics of natural conversations between naïve adult confederates and school-aged children with or without autism, with the goal of improving our understanding of conversational behavior in autistic girls and ultimately improving identification. METHODS: Forty-five school-aged children with autism (29 boys and 16 girls) and 47 non-autistic/neurotypical (NT) children (23 boys and 24 girls) engaged in a 5-min "get-to-know-you" conversation with a young adult confederate that was unaware of children's diagnostic status. Groups were matched on IQ estimates. Recordings were time-aligned and orthographically transcribed by trained annotators. Several speech and pause measures were calculated. Groups were compared using analysis of covariance models, controlling for age. RESULTS: Autistic girls used significantly more words than autistic boys, and produced longer speech segments than all other groups. Autistic boys spoke more slowly than NT children, whereas autistic girls did not differ from NT children in total word counts or speaking rate. Autistic boys interrupted confederates' speech less often and produced longer between-turn pauses (i.e., responded more slowly when it was their turn) compared to other children. Within-turn pause duration did not differ by group. LIMITATIONS: Our sample included verbally fluent children and adolescents aged 6-15 years, so our study results may not replicate in samples of younger children, adults, and individuals who are not verbally fluent. The results of this relatively small study, while compelling, should be interpreted with caution and replicated in a larger sample. CONCLUSION: This study investigated the temporal dynamics of everyday conversations and demonstrated that autistic girls and boys have distinct natural language profiles. Specifying differences in verbal communication lays the groundwork for the development of sensitive screening and diagnostic tools to more accurately identify autistic girls, and could inform future personalized interventions that improve short- and long-term social communication outcomes for all autistic children.


Assuntos
Transtorno Autístico , Adolescente , Humanos , Criança , Masculino , Feminino , Transtorno Autístico/diagnóstico , Caracteres Sexuais , Comunicação , Idioma , Fala
11.
Proc Natl Acad Sci U S A ; 106(14): 5859-64, 2009 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-19321416

RESUMO

The adult human distal gut microbial community is typically dominated by 2 bacterial phyla (divisions), the Firmicutes and the Bacteroidetes. Little is known about the factors that govern the interactions between their members. Here, we examine the niches of representatives of both phyla in vivo. Finished genome sequences were generated from Eubacterium rectale and E. eligens, which belong to Clostridium Cluster XIVa, one of the most common gut Firmicute clades. Comparison of these and 25 other gut Firmicutes and Bacteroidetes indicated that the Firmicutes possess smaller genomes and a disproportionately smaller number of glycan-degrading enzymes. Germ-free mice were then colonized with E. rectale and/or a prominent human gut Bacteroidetes, Bacteroides thetaiotaomicron, followed by whole-genome transcriptional profiling, high-resolution proteomic analysis, and biochemical assays of microbial-microbial and microbial-host interactions. B. thetaiotaomicron adapts to E. rectale by up-regulating expression of a variety of polysaccharide utilization loci encoding numerous glycoside hydrolases, and by signaling the host to produce mucosal glycans that it, but not E. rectale, can access. E. rectale adapts to B. thetaiotaomicron by decreasing production of its glycan-degrading enzymes, increasing expression of selected amino acid and sugar transporters, and facilitating glycolysis by reducing levels of NADH, in part via generation of butyrate from acetate, which in turn is used by the gut epithelium. This simplified model of the human gut microbiota illustrates niche specialization and functional redundancy within members of its major bacterial phyla, and the importance of host glycans as a nutrient foundation that ensures ecosystem stability.


Assuntos
Bacteroidetes/metabolismo , Ecossistema , Eubacterium/metabolismo , Intestinos/microbiologia , Animais , Bacteroidetes/citologia , Eubacterium/citologia , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Genoma Bacteriano , Humanos , Redes e Vias Metabólicas/genética , Camundongos , Modelos Biológicos , Dados de Sequência Molecular , Polissacarídeos/metabolismo , Simbiose
12.
Mol Autism ; 13(1): 5, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35012645

RESUMO

BACKGROUND: Autistic individuals frequently experience social communication challenges. Girls are diagnosed with autism less often than boys even when their symptoms are equally severe, which may be due to insufficient understanding of the way autism manifests in girls. Differences in the behavioral presentation of autism, including how people talk about social topics, could contribute to these persistent problems with identification. Despite a growing body of research suggesting that autistic girls and boys present distinct symptom profiles in a variety of domains, including social attention, friendships, social motivation, and language, differences in the way that autistic boys and girls communicate verbally are not yet well understood. Closely analyzing boys' and girls' socially-focused language during semi-structured clinical assessments could shed light on potential sex differences in the behavioral presentation of autistic individuals that may prove useful for identifying and effectively supporting autistic girls. Here, we compare social word use in verbally fluent autistic girls and boys during the interview sections of the ADOS-2 Module 3 and measure associations with clinical phenotype. METHODS: School-aged girls and boys with autism (N = 101, 25 females; aged 6-15) were matched on age, IQ, and parent/clinician ratings of autism symptom severity. Our primary analysis compared the number of social words produced by autistic boys and girls (normalized to account for differences in total word production). Social words are words that make reference to other people, including friends and family. RESULTS: There was a significant main effect of sex on social word production, such that autistic girls used more social words than autistic boys. To identify the specific types of words driving this effect, additional subcategories of friend and family words were analyzed. There was a significant effect of sex on friend words, with girls using significantly more friend words than boys. However, there was no significant main effect of sex on family words, suggesting that sex differences in social word production may be driven by girls talking more about friends compared to boys, not family. To assess relationships between word use and clinical phenotype, we modeled ADOS-2 Social Affect (SA) scores as a function of social word production. In the overall sample, social word use correlated significantly with ADOS-2 SA scores, indicating that participants who used more social words were rated as less socially impaired by clinicians. However, when examined in each sex separately, this result only held for boys. LIMITATIONS: This study cannot speak to the ways in which social word use may differ for younger children, adults, or individuals who are not verbally fluent; in addition, there were more autistic boys than girls in our sample, making it difficult to detect small effects. CONCLUSIONS: Autistic girls used significantly more social words than boys during a diagnostic assessment-despite being matched on age, IQ, and both parent- and clinician-rated autism symptom severity. Sex differences in linguistic markers of social phenotype in autism are especially important in light of the late or missed diagnoses that disproportionately affect autistic girls. Specifically, heightened talk about social topics could complicate autism referral and diagnosis when non-clinician observers expect a male-typical pattern of reduced social focus, which autistic girls may not always exhibit.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Transtorno do Espectro Autista/diagnóstico , Transtorno Autístico/diagnóstico , Criança , Feminino , Amigos , Humanos , Idioma , Masculino , Caracteres Sexuais , Fatores Sexuais
13.
Autism Res ; 15(6): 1090-1108, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35199482

RESUMO

Successful social communication is complex; it relies on effectively deploying and continuously revising one's behavior to fit the needs of a given conversation, partner, and context. For example, a skilled conversationalist may instinctively become less talkative with a quiet partner and more talkative with a chattier one. Prior research suggests that behavioral flexibility across social contexts can be a particular challenge for individuals with autism spectrum condition (ASC), and that difficulty adapting to the changing needs of a conversation contributes to communicative breakdowns and poor social outcomes. In this study, we examine whether reduced conversational adaptation, as measured by talkativeness, differentiates 48 verbally fluent children and teens with ASC from 50 neurotypical (NT) peers matched on age, intelligence quotient, and sex ratio. Participants completed the Contextual Assessment of Social Skills with two novel conversation partners. The first acted interested in the conversation and talked more (Interested condition), while the second acted bored and talked less (Bored condition). Results revealed that NT participants emulated their conversation partner's behavior by being more talkative in the Interested condition as compared to the Bored condition (z = 9.92, p < 0.001). In contrast, the ASC group did not differentially adapt their behavior to the Bored versus Interested context, instead remaining consistently talkative in both (p = 0.88). The results of this study have implications for understanding social communication and behavioral adaptation in ASC, and may be valuable for clinicians interested in improving conversational competence in verbally fluent individuals with autism. LAY SUMMARY: Social communication-including everyday conversations-can be challenging for individuals on the autism spectrum. In successful conversations, people tend to adjust aspects of their language to be more similar to their partners'. In this study, we found that children and teens with autism did not change their own talkativeness in response to a social partner who was more or less talkative, whereas neurotypical peers did. These findings have clinical implications for improving conversational competence in verbally fluent individuals with autism.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Adolescente , Criança , Comunicação , Humanos , Idioma , Habilidades Sociais
14.
J Diabetes Complications ; 35(3): 107843, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33419633

RESUMO

AIMS: Pancreatic beta-cell lipo-dysfunction decreases insulin secretion and predisposes to the development of type 2 diabetes. Through targeted Pex11ß knockdown and peroxisome depletion, our aim was to investigate the specific contribution of peroxisomes to palmitate mediated pancreatic beta-cell dysfunction. METHODS: MIN6 cells were transfected with probes targeted against Pex11ß, a regulator of peroxisome abundance, or with scrambled control probes. Peroxisome abundance was measured by PMP-70 protein expression. 48 h post transfection, cells were incubated with 250 µM palmitate or BSA control for a further 48 h before measurement of glucose stimulated insulin secretion and of reactive oxygen species. RESULTS: Pex11ß knockdown decreased target gene expression by >80% compared with the scrambled control (P<0.001). This led to decreased PMP-70 expression (p<0.01) and a 22% decrease in peroxisome number (p<0.05). At 25 mM glucose, palmitate treatment decreased insulin secretion by 64% in the scrambled control cells (2.54±0.25 vs 7.07±0.83 [mean±SEM] ng/h/µg protein; Palmitate vs BSA P<0.001), but by just 37% in the Pex11ß knockdown cells. Comparing responses in the presence of palmitate, insulin secretion at 25 mM glucose was significantly greater in the Pex11ß knockdown cells compared with the scrambled controls (4.04±0.46 vs 2.54±0.25 ng/h/µg protein; p<0.05). Reactive oxygen species generation with palmitate was lower in the Pex11ß knockdown cells compared with the scrambled controls (P<0.001). CONCLUSION: Pex11ß knockdown decreased peroxisome abundance, decreased palmitate mediated reactive oxygen species generation, and reversed the inhibitory effect of palmitate on insulin secretion. These findings reveal a distinct role of peroxisomes in palmitate mediated beta-cell dysfunction.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina/patologia , Peroxissomos , Animais , Linhagem Celular , Diabetes Mellitus Tipo 2/genética , Técnicas de Silenciamento de Genes , Glucose , Insulina , Proteínas de Membrana/genética , Camundongos , Palmitatos , Espécies Reativas de Oxigênio
15.
Eur J Obstet Gynecol Reprod Biol ; 252: 526-533, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32586597

RESUMO

Group B Streptococcus, a common commensal in the gut of humans and in the lower genital tract in women, remains an important cause of neonatal mortality and morbidity. The incidence of early onset disease has fallen markedly in countries that test women for carriage at 35-37 weeks of pregnancy and then offer intrapartum prophylaxis with penicillin during labour. Countries that do not test, but instead employ a risk factor approach, have not seen a similar fall. There are concerns about the effect on the neonatal microbiome of widespread use of antibiotic prophylaxis during labour, but so far the effects seem minor and temporary. Vaccination against GBS would be acceptable to most women and GBS vaccines are in the early stages of development. Tweetable abstract: Group B Strep is a key cause of infection, death and disability in young babies. Antibiotics given in labour remain the mainstay of prevention, until a vaccine is available.


Assuntos
Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mães , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus agalactiae
16.
PLoS One ; 15(1): e0226817, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978082

RESUMO

BACKGROUND: A large proportion of neonates are treated for presumed bacterial sepsis with broad spectrum antibiotics even though their blood cultures subsequently show no growth. This study aimed to investigate PCR-based methods to identify pathogens not detected by conventional culture. METHODS: Whole blood samples of 208 neonates with suspected early onset sepsis were tested using a panel of multiplexed bacterial PCRs targeting Streptococcus pneumoniae, Streptococcus agalactiae (GBS), Staphylococcus aureus, Streptococcus pyogenes (GAS), Enterobacteriaceae, Enterococcus faecalis, Enterococcus faecium, Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium, a 16S rRNA gene broad-range PCR and a multiplexed PCR for Candida spp. RESULTS: Two-hundred and eight samples were processed. In five of those samples, organisms were detected by conventional culture; all of those were also identified by PCR. PCR detected bacteria in 91 (45%) of the 203 samples that did not show bacterial growth in culture. S. aureus, Enterobacteriaceae and S. pneumoniae were the most frequently detected pathogens. A higher bacterial load detected by PCR was correlated positively with the number of clinical signs at presentation. CONCLUSION: Real-time PCR has the potential to be a valuable additional tool for the diagnosis of neonatal sepsis.


Assuntos
Bactérias/isolamento & purificação , Infecções Bacterianas/diagnóstico , Candida/isolamento & purificação , Candidíase/diagnóstico , Sepse Neonatal/microbiologia , RNA Ribossômico 16S/genética , Idade de Início , Bactérias/genética , Candida/genética , DNA Ribossômico/genética , Diagnóstico Precoce , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Enterococcus/genética , Enterococcus/isolamento & purificação , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido Prematuro , Reação em Cadeia da Polimerase Multiplex , Mycoplasma/genética , Mycoplasma/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Streptococcus/genética , Streptococcus/isolamento & purificação , Ureaplasma/genética , Ureaplasma/isolamento & purificação
17.
Am J Med Genet A ; 149A(8): 1795-800, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19610079

RESUMO

We present the longest known surviving case of a male infant with a mosaic complete trisomy 1q. Born at 39 weeks of gestation with respiratory distress, his weight was 3,330 g (25th centile); he had micrognathia, a posterior cleft of palate, abnormal ears and left thumb, syndactyly, and an absent corpus callosum. Initial blood karyotype was normal (46,XY). He died at age 5 months. Autopsy suggested aspiration as the primary cause of death and confirmed the antemortem findings of an absent corpus callosum and atrial septal defect. It also identified some central nervous system, cardiac, gastrointestinal, and lung anomalies not previously recognized. Cytogenetic analysis of skin fibroblasts obtained at autopsy showed a de novo unbalanced translocation between chromosomes 1 and 22: 46,XY,+1,der(1;22)(q10;q10)[25]/46,XY[65] in the cells examined. The previously reported cases had a similar phenotype with birth weight above the 50th centile for gestational age, small mouth, micrognathia, abnormal ears, abnormal fingers, microphthalmia, and hydrocephalus. The present case and a review of the literature delineates the phenotype in trisomy 1q, and reinforces the critical importance of effective communication between specialists, and obtaining permission for autopsy and skin biopsy, in the pursuit of a diagnosis.


Assuntos
Cromossomos Humanos Par 1/genética , Mosaicismo , Trissomia/genética , Encéfalo/patologia , Bandeamento Cromossômico , Cromossomos Humanos Par 22/genética , Evolução Fatal , Humanos , Lactente , Recém-Nascido , Masculino , Metáfase , Análise de Sobrevida , Sindactilia
19.
Arch Dis Child Fetal Neonatal Ed ; 103(6): F547-F553, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29208666

RESUMO

OBJECTIVE: To describe the epidemiology of neonatal infection over the past decade in UK neonatal units. DESIGN: Retrospective analysis of prospectively collected infection surveillance network data from 2005 to 2014. SETTING: 30 neonatal units in the UK. PATIENTS: Newborns on participating neonatal units who had a positive blood, cerebrospinal fluid or urine culture and were treated with at least 5 days of appropriate antibiotics. RESULTS: 2171 episodes of neonatal infection in 1922 infants were recorded. The incidence of infection was 6.1/1000 live births and 48.8/1000 neonatal admissions (2.9 and 23.5 respectively if coagulase-negative staphylococci (CoNS) cultures excluded). The incidence of infection showed a statistically significant reduction over time with reductions in the rates of both early-onset sepsis (EOS) and late-onset sepsis (LOS).The majority of episodes (76%) represented LOS (diagnosed > 48 hours after birth), and infection was more common in premature (<37 weeks gestation) and low birth weight (<2500 g) neonates (84% and 81%, respectively). Commonly identified pathogens included group B streptococci (43%) and Escherichia coli (18%) for EOS, while E. coli (15%), Staphylococcus aureus (14%) and CoNS were prominent causes of LOS. CONCLUSIONS: This paper describes the epidemiology of neonatal infection in the UK over the past decade. These data enable benchmarking of practice and inform areas of future research and guideline development. The results support the hypothesis that the introduction of infection prevention care bundles and antibiotic stewardship programmes in the UK has reduced the burden of LOS.


Assuntos
Antibacterianos/uso terapêutico , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Sepse Neonatal/epidemiologia , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/microbiologia , Estudos Retrospectivos , Reino Unido/epidemiologia
20.
Arch Dis Child Fetal Neonatal Ed ; 103(5): F474-F478, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29074716

RESUMO

OBJECTIVE: To define the susceptibilities of the common causative pathogens of neonatal sepsis in the UK. DESIGN: Retrospective analysis of the prospectively collected neonIN infection surveillance network data between 2005 and 2014. SETTING: 30 neonatal units in the UK. PATIENTS: Newborns admitted to participating neonatal units who return a positive blood, cerebrospinal fluid or urine culture and are treated with at least 5 days of appropriate antibiotics. RESULTS: 1568 isolates with recorded antimicrobial data were collected including 328 early-onset sepsis (EOS) isolates and 1240 late-onset sepsis (LOS) isolates. The majority of EOS pathogens (>92%) were susceptible to the four empirical commonly used antimicrobial combinations (eg, 93% for benzylpenicillin/gentamicin), while LOS pathogens demonstrated higher levels of resistance (eg, 89% for flucloxacillin/gentamicin). Among infants<1500 g and <32 weeks gestation, an amoxicillin/gentamicin combination demonstrated a trend towards improved coverage of EOS isolates than benzylpenicillin/gentamicin (93% vs 86%, p=0.211). CONCLUSIONS: This analysis provides insights into the patterns of antimicrobial resistance among UK neonatal pathogens. These data will inform areas of future research and can be used to update national evidence-based guidelines on antimicrobial usage.


Assuntos
Antibacterianos , Bactérias , Controle de Infecções , Sepse Neonatal , Antibacterianos/classificação , Antibacterianos/uso terapêutico , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Farmacorresistência Bacteriana , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Masculino , Testes de Sensibilidade Microbiana/métodos , Sepse Neonatal/diagnóstico , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/epidemiologia , Sepse Neonatal/microbiologia , Estudos Retrospectivos , Reino Unido/epidemiologia
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