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BACKGROUND: 20-25% pregnant women in the UK carry group B streptococcus (GBS) which, if left undetected, is transmitted from pregnant mothers to their babies during birth in 36% of cases. This transmission leads to early onset GBS infection (EOGBS) in 1% of babies which is a significant cause of mortality and morbidity in newborns. The literature available suggests women's knowledge of GBS is low, with many women unaware of the GBS bacterium. In addition, attitudes towards GBS testing have not been widely examined, with research mostly focusing on attitudes towards potential GBS vaccination. AIM: To examine women's knowledge of GBS in pregnancy and their attitudes towards GBS testing. METHODS: Semi-structured interviews with 19 women (5 pregnant and 14 postpartum). Interviews were transcribed and analysed using systematic thematic analysis. RESULTS: Four main theme categories were identified. Participants had varying levels of awareness of GBS, with the information provided by health professionals not being clearly explained or the importance of GBS being downplayed. Participants wanted more information and to feel informed. Overall, the majority had positive attitudes towards being offered and taking up GBS testing, and this study identified some of the key factors influencing their decision. These included: seeing GBS testing as just another routine procedure during pregnancy; that it would lower the risk of their baby becoming unwell; provide reassurance; and allow them to prepare; and provide informed choices. Participants also expressed a few common concerns about GBS testing: questioning the invasiveness of the procedure; risks to themselves and the baby; and the risk of receiving antibiotics. CONCLUSIONS: Women need clear, detailed information about GBS and GBS testing, and women's concerns are important to address if routine GBS testing is implemented. The efficacy of implementing routine universal testing in the UK is currently being investigated in a large multi-centre clinical trial; the GBS3trial, further qualitative research is needed to look at the acceptability of different methods of GBS testing, as well as the acceptability of GBS testing to women in specific groups, such as those planning a home birth or those from different ethnic backgrounds.
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Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , Gravidez , Feminino , Recém-Nascido , Humanos , Complicações Infecciosas na Gravidez/diagnóstico , Gestantes , Pesquisa Qualitativa , Parto , Streptococcus agalactiae , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/prevenção & controleRESUMO
Since early 2020, disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, causing millions of infections and deaths worldwide. Despite rapid deployment of effective vaccines, it is apparent that the global community lacks multipronged interventions to combat viral infection and disease. A major limitation is the paucity of antiviral drug options representing diverse molecular scaffolds and mechanisms of action. Here we report the antiviral activities of three distinct marine natural productsâhomofascaplysin A (1), (+)-aureol (2), and bromophycolide A (3)âevidenced by their ability to inhibit SARS-CoV-2 replication at concentrations that are nontoxic toward human airway epithelial cells. These compounds stand as promising candidates for further exploration toward the discovery of novel drug leads against SARS-CoV-2.
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Produtos Biológicos , Tratamento Farmacológico da COVID-19 , Antivirais/farmacologia , Produtos Biológicos/farmacologia , Células Epiteliais , Humanos , SARS-CoV-2RESUMO
Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing but relatively intact activities of daily living. MCI is a risk state for further cognitive and functional decline with 5-15% of people developing dementia per year. However, ~50% remain stable at 5 years and in a minority, symptoms resolve over time. There is considerable debate about whether MCI is a useful clinical diagnosis, or whether the use of the term prevents proper inquiry (by history, examination and investigations) into underlying causes of cognitive symptoms, which can include prodromal neurodegenerative disease, other physical or psychiatric illness, or combinations thereof. Cognitive testing, neuroimaging and fluid biomarkers can improve the sensitivity and specificity of aetiological diagnosis, with growing evidence that these may also help guide prognosis. Diagnostic criteria allow for a diagnosis of Alzheimer's disease to be made where MCI is accompanied by appropriate biomarker changes, but in practice, such biomarkers are not available in routine clinical practice in the UK. This would change if disease-modifying therapies became available and required a definitive diagnosis but would present major challenges to the National Health Service and similar health systems. Significantly increased investment would be required in training, infrastructure and provision of fluid biomarkers and neuroimaging. Statistical techniques combining markers may provide greater sensitivity and specificity than any single disease marker but their practical usefulness will depend on large-scale studies to ensure ecological validity and that multiple measures, e.g. both cognitive tests and biomarkers, are widely available for clinical use. To perform such large studies, we must increase research participation amongst those with MCI.
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Doença de Alzheimer , Disfunção Cognitiva , Doenças Neurodegenerativas , Atividades Cotidianas , Peptídeos beta-Amiloides , Biomarcadores , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Consenso , Progressão da Doença , Humanos , Testes Neuropsicológicos , Fragmentos de Peptídeos , Medicina EstatalRESUMO
A new cyclic peptide, kakeromamide B (1), and previously described cytotoxic cyanobacterial natural products ulongamide A (2), lyngbyabellin A (3), 18E-lyngbyaloside C (4), and lyngbyaloside (5) were identified from an antimalarial extract of the Fijian marine cyanobacterium Moorea producens. Compounds 1 and 1 exhibited moderate activity against Plasmodium falciparum blood-stages with EC50 values of 0.89 and 0.99 µM, respectively, whereas 3 was more potent with an EC50 value of 0.15 nM, respectively. Compounds 1, 4, and 5 displayed moderate liver-stage antimalarial activity against P. berghei liver schizonts with EC50 values of 1.1, 0.71, and 0.45 µM, respectively. The threading-based computational method FINDSITEcomb2.0 predicted the binding of 1 and 2 to potentially druggable proteins of Plasmodiumfalciparum, prompting formulation of hypotheses about possible mechanisms of action. Kakeromamide B (1) was predicted to bind to several Plasmodium actin-like proteins and a sortilin protein suggesting possible interference with parasite invasion of host cells. When 1 was tested in a mammalian actin polymerization assay, it stimulated actin polymerization in a dose-dependent manner, suggesting that 1 does, in fact, interact with actin.
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Antimaláricos/farmacologia , Cianobactérias , Peptídeos Cíclicos/farmacologia , Policetídeos/farmacologia , Antimaláricos/química , Produtos Biológicos , Fiji , Humanos , Oceanos e Mares , Peptídeos Cíclicos/química , Plasmodium falciparum/efeitos dos fármacos , Policetídeos/químicaRESUMO
A series of oligomeric phenols including the known natural product 3,4,3',4'-tetrahydroxy-1,1'-biphenyl (3), the previously synthesized 2,3,8,9-tetrahydroxybenzo[ c]chromen-6-one (4), and eight new related natural products, cladophorols B-I (5-12), were isolated from the Fijian green alga Cladophora socialis and identified by a combination of NMR spectroscopy, mass spectrometric analysis, and computational modeling using DFT calculations. J-resolved spectroscopy and line width reduction by picric acid addition aided in resolving the heavily overlapped aromatic signals. A panel of Gram-positive and Gram-negative pathogens used to evaluate pharmacological potential led to the determination that cladophorol C (6) exhibits potent antibiotic activity selective toward methicillin-resistant Staphylococcus aureus (MRSA) with an MIC of 1.4 µg/mL. Cladophorols B (5) and D-H (7-11) had more modest but also selective antibiotic potency. Activities of cladophorols A-I (4-12) were also assessed against the asexual blood stages of Plasmodium falciparum and revealed cladophorols A (4) and B (5) to have modest activity with EC50 values of 0.7 and 1.9 µg/mL, respectively.
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Antibacterianos/química , Antibacterianos/farmacologia , Clorófitas/química , Polimerização , Polifenóis/química , Polifenóis/farmacologia , Teoria da Densidade Funcional , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Ácido Vanílico/químicaRESUMO
Two sulfated diterpene glycosides featuring a highly substituted and sterically encumbered cyclopropane ring have been isolated from the marine red alga Peyssonnelia sp. Combination of a wide array of 2D NMR spectroscopic experiments, in a systematic structure elucidation workflow, revealed that peyssonnosides A-B (1-2) represent a new class of diterpene glycosides with a tetracyclo [7.5.0.01,10.05,9] tetradecane architecture. A salient feature of this workflow is the unique application of quantitative interproton distances obtained from the rotating frame Overhauser effect spectroscopy (ROESY) NMR experiment, wherein the ß-d-glucose moiety of 1 was used as an internal probe to unequivocally determine the absolute configuration, which was also supported by optical rotatory dispersion (ORD). Peyssonnoside A (1) exhibited promising activity against liver stage Plasmodium berghei and moderate antimethicillin-resistant Staphylococcus aureus (MRSA) activity, with no cytotoxicity against human keratinocytes. Additionally, 1 showed strong growth inhibition of the marine fungus Dendryphiella salina indicating an antifungal ecological role in its natural environment. The high natural abundance and novel carbon skeleton of 1 suggests a rare terpene cyclase machinery, exemplifying the chemical diversity in this phylogenetically distinct marine red alga.
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Diterpenos/síntese química , Glicosídeos/síntese química , Rodófitas/química , Análise Espectral/métodos , Organismos Aquáticos , Modelos Moleculares , Estrutura MolecularRESUMO
Correction for 'Recent trends in the structural revision of natural products' by Bhuwan Khatri Chhetri et al., Nat. Prod. Rep., 2018, 35, 514-531.
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Covering: 2012 to 2017 This article reviews recent reports on the structural revision of natural products. Through a critical assessment of the original and revised published structures, the article addresses why each structure was targeted for revision, discusses the techniques and key discrepancies that led to the proposal of the revised structure, and offers measures that may have been taken during the original structure determination to prevent error. With the revised structures in hand, weaknesses of original proposals are assessed, providing a better understanding on the logic behind structure determination.
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Produtos Biológicos/química , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Estrutura Molecular , EstereoisomerismoRESUMO
BACKGROUND: The US federal regulation "Exception from Informed Consent for Emergency Research," 21 Code of Federal Regulations 50.24, permits emergency research without informed consent under limited conditions. Additional safeguards to protect human subjects include requirements for community consultation and public disclosure prior to starting the research. Because the regulations are vague about these requirements, Institutional Review Boards determine the adequacy of these activities at a local level. Thus, there is potential for broad interpretation and practice variation. AIM: To describe the variation of community consultation and public disclosure activities approved by Institutional Review Boards, and the effectiveness of this process for a multi-center, Exception from Informed Consent, pediatric status epilepticus clinical research trial. METHODS: Community consultation and public disclosure activities were analyzed for each of the 15 participating sites. Surveys were conducted with participants enrolled in the status epilepticus trial to assess the effectiveness of public disclosure dissemination prior to study enrollment. RESULTS: Every Institutional Review Board, among the 15 participating sites, had a varied interpretation of Exception from Informed Consent regulations for community consultation and public disclosure activities. Institutional Review Boards required various combinations of focus groups, interviews, surveys, and meetings for community consultation, and news releases, mailings, and public service announcements for public disclosure. At least 4335 patients received information about the study from these efforts. In all, 158 chose to be included in the "Opt Out" list. Of the 304 participants who were enrolled under Exception from Informed Consent, 12 (5%) had heard about the study through community consultation or public disclosure activities. The activities reaching the highest number of participants were surveys and focus groups associated with existing meetings. Public disclosure activities were more efficient and cost-effective if they were part of an in-hospital resource for patients and families. CONCLUSION: There is substantial variation in Institutional Review Boards' interpretations of the federal regulations for community consultation and public disclosure. One of the goals of community consultation and public disclosure efforts for emergency research is to provide community members an opportunity to opt out of Exception from Informed Consent research; however, rarely do patients or their legally authorized representatives report having learned about a study prior to enrollment.
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Revelação/legislação & jurisprudência , Consentimento Livre e Esclarecido/legislação & jurisprudência , Estudos Multicêntricos como Assunto/métodos , Pediatria , Ensaios Clínicos Controlados Aleatórios como Assunto/legislação & jurisprudência , Adolescente , Pesquisa Biomédica/legislação & jurisprudência , Criança , Pré-Escolar , Método Duplo-Cego , Serviços Médicos de Emergência/legislação & jurisprudência , Serviços Médicos de Emergência/organização & administração , Feminino , Grupos Focais , Humanos , Lactente , Recém-Nascido , Masculino , Vigilância da População , Encaminhamento e Consulta/organização & administração , Projetos de Pesquisa , Consentimento do Representante Legal/legislação & jurisprudência , Estados UnidosRESUMO
BACKGROUND: Group B streptococcus (GBS) is a bacterium carried by 20-25 % of pregnant women in the UK, which can be transmitted from pregnant women to their babies at the time of birth. Women can be tested for GBS in pregnancy using a vaginal-rectal swab, however, this testing is currently not routinely offered in the UK. A large clinical trial is underway to determine the clinical and cost-effectiveness of routine testing (ISRCTN reference number ISRCTN49639731). A crucial part of understanding whether this type of test should be implemented is women's views on the acceptability of being offered GBS tests, their preferences towards testing procedures and their willingness to receive these tests. AIM: To explore women's views on the acceptability of different methods of Group B streptococcal bacteria (GBS) testing in pregnancy, including self-swabbing procedures. METHODS: A convenience sample of 19 women (5 pregnant and 14 postpartum) were interviewed using a semi-structured interview guide. Interviews were transcribed and analysed using systematic thematic analysis. RESULTS: Findings show that many of the women interviewed were not concerned about being offered a GBS test, were willing to provide a sample and felt positive towards samples being taken to detect GBS. Women varied in their preferences on the best time for sampling. Some thought being approached during pregnancy gave them time to understand the purpose of testing, prepare for what may happen next and ask questions about potential treatment if needed. Others thought labour was a good time to provide accurate results on GBS carriage at birth and reduce unnecessary worry during pregnancy. However, women were concerned that they may be unable to make an informed decision in labour due to time, pain and the prospect of birthing quickly. Women perceived clinician swabbing as more accurate than self-sampling; however, many thought clinician swabbing might be embarrassing so self-swabs should be available to increase uptake for some women. CONCLUSIONS: Overall, women thought both pregnancy and labour were acceptable times to test for GBS. The majority found both clinician and self-swabbing procedures acceptable; however, many had a preferred swabbing option and thought women should be given the choice of the swabbing procedure most acceptable to them. It is important that women are given information about GBS testing and its procedures in pregnancy regardless of when the GBS swabbing is performed.
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Pesquisa Qualitativa , Infecções Estreptocócicas , Streptococcus agalactiae , Humanos , Feminino , Gravidez , Infecções Estreptocócicas/diagnóstico , Adulto , Reino Unido , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Complicações Infecciosas na Gravidez/diagnóstico , Manejo de Espécimes/métodos , Gestantes/psicologiaRESUMO
OBJECTIVES: To establish a James Lind Alliance (JLA) Priority Setting Partnership (PSP) to identify research priorities relevant to the health and social care needs of adults with lived experience of recent and/or historical sexual violence/abuse. PARTICIPANTS: Adults (aged 18+ years) with lived experience of sexual violence/abuse (ie, 'survivors') were consulted for this PSP, alongside healthcare and social care professionals who support survivors across the public, voluntary, community, independent practice and social enterprise sectors. METHODS: In line with standard JLA PSP methodology, participants completed an initial online survey to propose research questions relevant to the health and social care needs of survivors. Research questions unanswered by current evidence were identified, and a second online survey was deployed to identify respondents' priorities from this list. Questions prioritised through the second survey were presented at a consensus meeting with key stakeholders to agree the top 10 research priorities using a modified nominal group technique approach. RESULTS: 223 participants (54% survivors) provided 484 suggested questions. Seventy-five unique questions unanswered by research were identified and subsequently ranked by 343 participants (60% survivors). A consensus meeting with 31 stakeholders (42% survivors) examined the top-ranking priorities from the second survey and agreed the top 10 research priorities. These included research into forms of support and recovery outcomes valued by survivors, how to best support people of colour/black, Asian and minority ethnic and lesbian, gay, bisexual, transgender, and queer (LGBTQ+) survivors, improving access to high-quality psychological therapies, reducing public misconceptions/stigma, the impact of involvement in the criminal justice system on well-being, and how physical and mental health services can become more 'trauma informed'. CONCLUSIONS: These research priorities identify crucial gaps in the existing evidence to better support adult survivors of sexual violence and abuse. Researchers and funders should prioritise further work in these priority areas identified by survivors and the professionals who support them.
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Delitos Sexuais , Minorias Sexuais e de Gênero , Adulto , Humanos , Bissexualidade , ConsensoRESUMO
Class switch recombination (CSR) is a region-specific, transcriptionally regulated, nonhomologous recombinational process that is initiated by activation-induced cytidine deaminase (AID). The initial lesions in the switch (S) regions are subsequently processed and resolved, leading to recombination of the two targeted S regions. The mechanisms by which repair and ligation of the broken DNA ends occurs is still elusive. Recently, a small number of patients lacking DNA ligase IV, a critical component of the nonhomologous end joining (NHEJ) machinery, have been identified. We show that these patients display a considerably increased donor/acceptor homology at Smu-Salpha junctions compared with healthy controls. In contrast, Smu-Sgamma junctions show an increased frequency of insertions but no increase in junctional homology. These altered patterns of junctional resolution may be related to differences in the homology between the Smu and the downstream isotype S regions, and could reflect different modes of switch junction resolution when NHEJ is impaired. These findings link DNA ligase IV, and thus NHEJ, to CSR.
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DNA Ligases/metabolismo , Switching de Imunoglobulina/genética , Recombinação Genética , Sequência de Bases , DNA Ligase Dependente de ATP , DNA Ligases/deficiência , DNA Ligases/genética , Humanos , Imunoglobulina A/genética , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Dados de Sequência Molecular , Mutação , Homologia de SequênciaRESUMO
The death of a child is a life-altering event for parents, leading to grief that is individual, intense, and long lasting. The grief experienced by parents following the death of their child can affect their relationships and as they sometimes see it, their role within society. Parents can find grief isolating, due to society's lack of understanding of their grief experience. Gendered differences in grief reactions have also been noted. Theoretical understandings of bereavement, now acknowledge parental need "not to let go" but rather to reconstruct relationships with their deceased child in terms of a continuing bond. This narrative literature review draws together theory and research on the topic, highlighting current knowledge and suggesting ways in which children's nurses can support parents as they live through the loss of their child.
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Adaptação Psicológica , Luto , Morte , Pais/psicologia , Criança , Humanos , Apoio SocialRESUMO
A susceptibility locus for bipolar affective disorder has been mapped to chromosome 4q35 in a large multigenerational pedigree. We have expanded this analysis to include 55 pedigrees (674 individuals, 214 affecteds). The evidence for linkage to 4q35 was strengthened in this larger cohort, with a maximum two-point LOD score of 3.2 for marker D4S1652. Several other markers in the region gave LOD scores greater than 1.5. Non-parametric analysis provided additional support for linkage to the 4q35 region. To further refine this region, haplotype analysis was carried out in 16 of the 55 pedigrees that showed evidence of linkage. As there is no evidence for an ancestral haplotype, nor a one-to-one correspondence between the disease and putative disease haplotype, we undertook an analysis based on pedigree-specific, identical-by-descent allele-sharing in order to define a probable disease region. This analysis indicated that the percentage sharing of alleles, identical-by-descent, in affecteds of all linked pedigrees increases from 60% at the centromeric markers to 75% for markers at the telomere. Maximal allele sharing occurred between markers D4S3051 and 4qTEL13 with this 24 cM region defining a probable disease region. We have constructed a physical map of the 4q35 interval consisting of a YAC contig and BAC clones. Based on this map the probable disease region between D4S3051 and 4qTEL13 corresponds to only 2.3 Mb. This region is very gene poor with only three known genes indicated from the YAC/BAC map. The small number of genes will facilitate systematic screening for variations associated with bipolar disorder.