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1.
Nucleic Acids Res ; 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39360614

RESUMO

Type III CRISPR immune systems bind viral or plasmid RNA transcripts and activate Csm3/Cmr4 and Cas10 nucleases to uniquely cleave both invader RNA and DNA, respectively. Additionally, type III effector complexes generate cyclic oligoadenylate (cOA) signaling molecules to activate trans-acting, auxiliary Csm6/Csx1 ribonucleases, previously proposed to be non-specific in their in vivo RNA cleavage preference. Despite extensive in vitro studies, the nuclease requirements of type III systems in their native contexts remain poorly understood. Here we systematically investigated the in vivo roles for immunity of each of the three Streptococcus thermophilus (Sth) type III-A Cas nucleases and cOA signaling by challenging nuclease defective mutant strains with plasmid and phage infections. Our results reveal that RNA cleavage by Csm6 is both sufficient and essential for maintaining wild-type levels of immunity. Importantly, Csm6 RNase activity leads to immunity against even high levels of phage challenge without causing host cell dormancy or death. Transcriptomic analyses during phage infection indicated Csm6-mediated and crRNA-directed preferential cleavage of phage transcripts. Our findings highlight the critical role of Csm6 RNase activity in type III immunity and demonstrate specificity for invader RNA transcripts by Csm6 to ensure host cell survival upon phage infection.

2.
Genome Res ; 31(4): 645-658, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33722935

RESUMO

We have developed periscope, a tool for the detection and quantification of subgenomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation of the SARS-CoV-2 RNA genome for most open reading frames (ORFs) occurs via RNA intermediates termed "subgenomic RNAs." sgRNAs are produced through discontinuous transcription, which relies on homology between transcription regulatory sequences (TRS-B) upstream of the ORF start codons and that of the TRS-L, which is located in the 5' UTR. TRS-L is immediately preceded by a leader sequence. This leader sequence is therefore found at the 5' end of all sgRNA. We applied periscope to 1155 SARS-CoV-2 genomes from Sheffield, United Kingdom, and validated our findings using orthogonal data sets and in vitro cell systems. By using a simple local alignment to detect reads that contain the leader sequence, we were able to identify and quantify reads arising from canonical and noncanonical sgRNA. We were able to detect all canonical sgRNAs at the expected abundances, with the exception of ORF10. A number of recurrent noncanonical sgRNAs are detected. We show that the results are reproducible using technical replicates and determine the optimum number of reads for sgRNA analysis. In VeroE6 ACE2+/- cell lines, periscope can detect the changes in the kinetics of sgRNA in orthogonal sequencing data sets. Finally, variants found in genomic RNA are transmitted to sgRNAs with high fidelity in most cases. This tool can be applied to all sequenced COVID-19 samples worldwide to provide comprehensive analysis of SARS-CoV-2 sgRNA.


Assuntos
Genoma Viral , RNA Viral/genética , SARS-CoV-2/genética , Análise de Sequência de RNA/métodos , Animais , Sequência de Bases , Chlorocebus aethiops , Humanos , Limite de Detecção , Células Vero
3.
Pacing Clin Electrophysiol ; 47(4): 533-541, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38477034

RESUMO

BACKGROUND: Optimization of atrial-ventricular delay (AVD) during atrial sensing (SAVD) and pacing (PAVD) provides the most effective cardiac resynchronization therapy (CRT). We demonstrate a novel electrocardiographic methodology for quantifying electrical synchrony and optimizing SAVD/PAVD. METHODS: We studied 40 CRT patients with LV activation delay. Atrial-sensed to RV-sensed (As-RVs) and atrial-paced to RV-sensed (Ap-RVs) intervals were measured from intracardiac electrograms (IEGM). LV-only pacing was performed over a range of SAVD/PAVD settings. Electrical dyssynchrony (cardiac resynchronization index; CRI) was measured at each setting using a multilead ECG system placed over the anterior and posterior torso. Biventricular pacing, which included multiple interventricular delays, was also conducted in a subset of 10 patients. RESULTS: When paced LV-only, peak CRI was similar (93 ± 5% vs. 92 ± 5%) during atrial sensing or pacing but optimal PAVD was 61 ± 31 ms greater than optimal SAVD. The difference between As-RVs and Ap-RVs intervals on IEGMs (62 ± 31 ms) was nearly identical. The slope of the correlation line (0.98) and the correlation coefficient r (0.99) comparing the 2 methods of assessing SAVD-PAVD offset were nearly 1 and the y-intercept (0.63 ms) was near 0. During simultaneous biventricular (BiV) pacing at short AVD, SAVD and PAVD programming did not affect CRI, but CRI was significantly (p < .05) lower during atrial sensing at long AVD. CONCLUSIONS: A novel methodology for measuring electrical dyssynchrony was used to determine electrically optimal SAVD/PAVD during LV-only pacing. When BiV pacing, shorter AVDs produce better electrical synchrony.


Assuntos
Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Humanos , Terapia de Ressincronização Cardíaca/métodos , Resultado do Tratamento , Ventrículos do Coração , Dispositivos de Terapia de Ressincronização Cardíaca , Átrios do Coração , Eletrocardiografia/métodos , Insuficiência Cardíaca/terapia
4.
J Bacteriol ; 205(6): e0048222, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37255445

RESUMO

Prokaryotes are under constant pressure from phage infection and thus have evolved multiple means of defense or evasion. While CRISPR-Cas constitutes a robust immune system and appears to be the predominant means of survival for Streptococcus thermophilus when facing lytic phage infection, other forms of phage resistance coexist in this species. Here, we show that S. thermophilus strains with deleted CRISPR-Cas loci can still give rise to phage-resistant clones following lytic phage challenge. Notably, non-CRISPR phage-resistant survivors had multiple mutations which would truncate or recode a membrane-anchored host protease, FtsH. Phage adsorption was dramatically reduced in FtsH mutants, implicating this protein in phage attachment. Phages were isolated which could bypass FtsH-based resistance through mutations predicted to alter tape measure protein translation. Together, these results identify key components in phage propagation that are subject to mutation in the molecular arms race between phage and host cell. IMPORTANCE Streptococcus thermophilus is an important organism for production of cultured dairy foods, but it is susceptible to lytic phages which can lead to failed products. Consequently, mechanisms for phage resistance are an active area of research. One such mechanism is CRISPR-Cas, and S. thermophilus is a model organism for the study of this form of adaptive immunity. Here, we expand on known mechanisms with our finding that spontaneous mutations in ftsH, a gene encoding a membrane-anchored protease, protected against phage infection by disrupting phage adsorption. In turn, mutations in phage tail protein genes allowed phages to overcome ftsH-based resistance. Our results identified components in phage propagation that are subject to mutation in the molecular arms race between phage and host.


Assuntos
Bacteriófagos , Fagos de Streptococcus , Bacteriófagos/genética , Streptococcus thermophilus/genética , Adsorção , Mutação , Peptídeo Hidrolases/genética , Sistemas CRISPR-Cas , Fagos de Streptococcus/genética
5.
Diabet Med ; 40(9): e15067, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36786059

RESUMO

AIMS: We aimed to quantify the use of person-first language (PFL) among scholarly articles focusing on diabetes or obesity. METHODS: PFL and condition-first language (CFL) terms for diabetes and obesity (e.g. diabetic, obese) were identified from existing guidelines and a review of the literature. Exact phrase literature searches were conducted between 2011 and 2020 and results were categorised as PFL, CFL or both. RESULTS: Among diabetes articles, 43% used PFL, 40% used CFL and 17% contained both. Among obesity articles, 0.5% used PFL, 99% used CFL and 0.2% used both. The use of PFL increased by 3% per year for diabetes articles, compared to 117% for obesity articles. The rate of adoption of PFL in diabetes articles was unchanged in 2018-2020 compared to the 3 years prior. CONCLUSIONS: While the use of person-first language in diabetes articles had increased over the review period, its rate of adoption has started to slow. Conversely, the use of PFL in obesity articles is nascent and increasing.


Assuntos
Diabetes Mellitus , Humanos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Obesidade/complicações , Obesidade/epidemiologia , Idioma
6.
Pediatr Emerg Care ; 39(12): 923-928, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36728119

RESUMO

OBJECTIVE: Mandible fractures are uncommon injuries in infants and young children and may raise concern for nonaccidental trauma. Our study describes several children with mandible fractures to identify features that might differentiate abuse from accident. METHODS: Records and imaging were reviewed for children aged 24 months and younger who were diagnosed with mandible fractures at 2 tertiary pediatric care centers. Twenty-one cases were included, 8 of whom had formal child abuse consultations. Cases were reviewed for mechanisms of injury, physical examination findings, and occult injuries identified, as well as the final abuse determination. RESULTS: Among children with child abuse consultations, 5 injuries (62.5%) were determined to be accidental, 1 (12.5%) was abusive, and 2 were indeterminate for abuse or accident (25%). In each accidentally injured child, the reported mechanism of injury was a short fall with evidence of facial impact. No accidentally injured child had unexpected occult injuries or noncraniofacial cutaneous injuries. CONCLUSIONS: Infants and young children can sometimes sustain mandible fractures accidentally after well-described short falls with evidence of facial impact. Abuse remains in the differential diagnosis, and children should be evaluated accordingly. We propose that accidental injury be considered when a well-evaluated child with an isolated mandible fracture has a history of a short fall.


Assuntos
Maus-Tratos Infantis , Fraturas Ósseas , Lactente , Humanos , Pré-Escolar , Criança , Maus-Tratos Infantis/diagnóstico , Mandíbula , Estudos Retrospectivos
7.
Pediatr Blood Cancer ; 69(7): e29722, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35441483

RESUMO

Infantile myofibroma is a rare, benign tumour of infancy typically managed surgically. In a minority of cases, more aggressive disease is seen and chemotherapy with vinblastine and methotrexate may be used, although evidence for this is limited. Chemotherapy dosing in infants is challenging, and vinblastine disposition in infants is unknown. We describe the use of vinblastine therapeutic drug monitoring in four cases of infantile myofibroma. Marked inter- and intrapatient variability was observed, highlighting the poorly understood pharmacokinetics of vinblastine in children, the challenges inherent in treating neonates, and the role of adaptive dosing in optimising drug exposure in challenging situations.


Assuntos
Miofibroma , Miofibromatose , Criança , Monitoramento de Medicamentos , Humanos , Lactente , Recém-Nascido , Miofibroma/tratamento farmacológico , Vimblastina
8.
J Clin Microbiol ; 59(6)2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-33782112

RESUMO

LamPORE is a novel diagnostic platform for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA combining loop-mediated isothermal amplification with nanopore sequencing, which could potentially be used to analyze thousands of samples per day on a single instrument. We evaluated the performance of LamPORE against reverse transcriptase PCR (RT-PCR) using RNA extracted from spiked respiratory samples and stored nose and throat swabs collected at two UK hospitals. The limit of detection of LamPORE was 10 genome copies/µl of extracted RNA, which is above the limit achievable by RT-PCR, but was not associated with a significant reduction of sensitivity in clinical samples. Positive clinical specimens came mostly from patients with acute symptomatic infection, and among them, LamPORE had a diagnostic sensitivity of 99.1% (226/228; 95% confidence interval [CI], 96.9% to 99.9%). Among negative clinical specimens, including 153 with other respiratory pathogens detected, LamPORE had a diagnostic specificity of 99.6% (278/279; 98.0% to 100.0%). Overall, 1.4% (7/514; 0.5% to 2.9%) of samples produced an indeterminate result on first testing, and repeat LamPORE testing on the same RNA extract had a reproducibility of 96.8% (478/494; 94.8% to 98.1%). LamPORE has a similar performance as RT-PCR for the diagnosis of SARS-CoV-2 infection in symptomatic patients and offers a promising approach to high-throughput testing.


Assuntos
COVID-19 , Sequenciamento por Nanoporos , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , RNA Viral/genética , Reprodutibilidade dos Testes , SARS-CoV-2 , Sensibilidade e Especificidade
9.
Pediatr Dermatol ; 38(4): 859-863, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34060140

RESUMO

BACKGROUND: Recognizable skin findings of child physical abuse include bruises, abrasions, lacerations, bite marks, burns, and oral injuries. Self-induced skin picking, or neurotic excoriation, can correspond to emotional stress, underlying psychiatric illness, or substance abuse. Parental neurotic excoriation injury of children has not been reported previously as a form of physical abuse. METHODS: We present a case series of five children abused via parental excoriation. All affected children were three years of age or younger and otherwise healthy. Each child presented with wounds determined to be consistent with chronic picking. Patient age, injury location, and in some cases, witness accounts confirmed the lesions were not self-inflicted. RESULTS: In three cases, caregivers reported methamphetamine use. In these cases, caregivers repeatedly picked or wiped the infants' skin. In two cases, the caregiver demonstrated personal neurotic excoriation behavior, which was imposed upon her children resulting in similar lesions. One affected child died at 14 days of age from abusive head trauma, while the other four children were placed in foster care by Child Protective Services. CONCLUSION: Excoriation injury places children at risk for significant scarring and other long-term effects. We report examples demonstrating that repetitive skin injury by caregivers is a diagnostic consideration for abuse in young children.


Assuntos
Maus-Tratos Infantis , Dermatite , Comportamento Autodestrutivo , Criança , Maus-Tratos Infantis/diagnóstico , Pré-Escolar , Feminino , Humanos , Lactente , Pais , Abuso Físico
10.
J Emerg Med ; 61(2): 198-204, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33795168

RESUMO

BACKGROUND: Bruising in an infant is an important sentinel injury that should raise concern for child physical abuse, and should prompt a medical evaluation for occult injury. Hyperflexion during forceful squeezing of an infant's hand results in a distinct pattern of bruising along the palmar and interdigital creases, as well as the palmar eminences. Self-inflicted injury by the infant or injury resulting from benign handling should not be accepted as plausible explanations for this injury. The presence of concurrent occult injuries is common, and further supports concerns for abuse. However, when this distinct pattern of palm bruising is identified in an infant, the absence of occult injuries should not prevent the recognition of child physical abuse. CASE REPORT: We report 11 cases depicting this distinct pattern of palm bruising in infants. Additionally, we include a perpetrator's documented confession. To the best of our knowledge, this pattern of bruising has not been previously described in the medical literature. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians play a crucial role in recognizing and addressing child physical abuse. Prompt recognition of this finding can aid in the identification of child physical abuse, even in the absence of underlying occult injury. This, in turn, can potentially prevent further injury, and even death, of an infant.


Assuntos
Maus-Tratos Infantis , Contusões , Criança , Maus-Tratos Infantis/diagnóstico , Contusões/etiologia , Humanos , Lactente , Abuso Físico
11.
12.
J Biomech Eng ; 140(9)2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29801173

RESUMO

Many people with amputation utilize a prosthetic device to maintain function and ambulation. During the use of the prosthetic device, their residual limbs can develop wounds called pressure ulcers. The formation of these wounds has been linked to deformation and loading conditions of the skin and deeper tissues. Our research objective was to develop a complete profile of displacements on the gel liner at the interface with the socket during walking in transtibial amputees. Displacements for seven regions along the limb were quantified in addition to six calculations of displacement and three rotations relative to the prosthetic socket. The largest displacements were observed in the distal region of the gel liner, near the pin locking mechanism on the gel liner. Displacements were uneven throughout the liner with distal regions showing higher displacements. This mechanics-based information, combined with clinical information, will allow us to understand the local skin and muscle displacements, and will provide insights regarding localized tissue breakdown. Knowledge of how the liner displaces within the prosthetic socket can also help prosthetists modify designs to reduce these displacements, and reduce the potential for shear on the skin and in deeper tissues.


Assuntos
Membros Artificiais , Joelho , Fenômenos Mecânicos , Amputação Cirúrgica , Fenômenos Biomecânicos , Géis , Humanos , Joelho/fisiologia , Pessoa de Meia-Idade , Movimento , Desenho de Prótese , Rotação , Estresse Mecânico
13.
J Emerg Med ; 55(4): 455-464, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30195946

RESUMO

BACKGROUND: Treatment for epistaxis includes application of intranasal vasoconstrictors. These medications have a precaution against use in patients with hypertension. Given that many patients who present with epistaxis are hypertensive, these warnings are commonly overridden by clinical necessity. OBJECTIVE: Our aim was to determine the effects of intranasal vasoconstrictors on blood pressure. METHODS: We conducted a single-center, randomized, double-blind, placebo-controlled trial from November 2014 through July 2016. Adult patients being discharged from the emergency department (ED) at Mayo Clinic (Rochester, Minnesota) were recruited. Patients were ineligible if they had a contraindication to study medications, had a history of hypertension, were currently taking antihypertensive or antidysrhythmic medications, or had nasal abnormalities, such as epistaxis. Subjects were randomized to one of four study arms (phenylephrine 0.25%; oxymetazoline 0.05%; lidocaine 1% with epinephrine 1:100,000; or bacteriostatic 0.9% sodium chloride [saline]). Blood pressure and heart rate were measured every 5 min for 30 min. RESULTS: Sixty-eight patients were enrolled in the study; of these, 63 patients completed the study (oxymetazoline, n = 15; phenylephrine, n = 20; lidocaine with epinephrine, n = 11; saline, n = 17). We did not observe any significant differences in mean arterial pressure over time between phenylephrine and saline, oxymetazoline and saline, or lidocaine with epinephrine and saline. The mean greatest increases from baseline in mean arterial pressure, systolic and diastolic blood pressure, and heart rate for each treatment group were also not significantly different from the saline group. CONCLUSIONS: Intranasal vasoconstrictors did not significantly increase blood pressure in patients without a history of hypertension. Our findings reinforce the practice of administering these medications to patients who present to the ED with epistaxis, regardless of high blood pressure.


Assuntos
Administração Intranasal , Pressão Sanguínea/efeitos dos fármacos , Epistaxe/tratamento farmacológico , Vasoconstritores/administração & dosagem , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Anestésicos Locais/uso terapêutico , Pressão Sanguínea/fisiologia , Método Duplo-Cego , Serviço Hospitalar de Emergência/organização & administração , Epinefrina/administração & dosagem , Epinefrina/farmacologia , Epinefrina/uso terapêutico , Epistaxe/etiologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Lidocaína/uso terapêutico , Masculino , Descongestionantes Nasais/administração & dosagem , Descongestionantes Nasais/farmacologia , Descongestionantes Nasais/uso terapêutico , Oximetazolina/administração & dosagem , Oximetazolina/farmacologia , Oximetazolina/uso terapêutico , Fenilefrina/administração & dosagem , Fenilefrina/farmacologia , Fenilefrina/uso terapêutico , Placebos , Cloreto de Sódio/administração & dosagem , Cloreto de Sódio/farmacologia , Cloreto de Sódio/uso terapêutico , Vasoconstritores/uso terapêutico
14.
Public Health Nurs ; 34(6): 522-530, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28812324

RESUMO

BACKGROUND: Adverse childhood experiences (ACEs) are associated with adult high-risk behaviors and diseases. There is value in screening parents for ACEs given the repercussions parental ACEs may have on parenting behaviors and child development. The primary aim of this study was to assess the feasibility of parental ACE screening in the home setting. A secondary aim was to evaluate whether or not maternal ACEs correlated with maternal mental health measures. METHODS: Two home visiting programs that support early childhood development and conduct parental mental health screening implemented ACE screening for parents of infants <1 year of age. Descriptive statistics were produced for population surveillance of ACEs as well as standard practice screens for depression, anxiety, substance use, and intimate partner violence. Logistic models were used to examine associations between ACE score and mental health measures. RESULTS: A total of 110 parents completed the ACE screen. All possible ACE score outcomes were represented (0-10). A trend toward association of positive prenatal maternal depression screen with ACE score was identified (p = .05). CONCLUSION: This novel prospective home-based screening program for parental ACEs was feasible and identified a trend toward increasing ACE score association with positive prenatal maternal depression screen.


Assuntos
Visita Domiciliar , Acontecimentos que Mudam a Vida , Programas de Rastreamento/métodos , Transtornos Mentais/diagnóstico , Pais/psicologia , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos
15.
Appetite ; 83: 263-268, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25218720

RESUMO

The purpose of this study was to examine whether or not the presence of an overweight eating companion influences healthy and unhealthy eating behavior, and to determine if the effect is moderated by how the companion serves herself. A professional actress either wore an overweight prosthesis (i.e., "fatsuit") or did not wear one, and served herself either healthily (i.e., a small amount of pasta and a large amount of salad) or unhealthily (i.e., a large amount of pasta and a small amount of salad) for lunch. After observing her, male and female participants were asked to serve themselves pasta and salad to eat. Results demonstrated that regardless of how the confederate served, participants served and ate a larger amount of pasta when she was wearing the prosthesis than when she was not. In addition, when the confederate served herself healthily, participants served and ate a smaller amount of salad when she was wearing the prosthesis than when she was not. Consistent with the "lower health commitment" hypothesis, these results demonstrated that people may eat larger portions of unhealthy food and smaller portions of healthy food when eating with an overweight person, probably because the health commitment goal is less activated. More generally, this study provides evidence that the body type of an eating companion, as well as whether she serves herself healthily or unhealthily, influences the quantity of food intake.


Assuntos
Beleza , Ingestão de Energia , Conhecimentos, Atitudes e Prática em Saúde , Hiperfagia/psicologia , Relações Interpessoais , Modelos Psicológicos , Sobrepeso/prevenção & controle , Adolescente , Adulto , Regulação do Apetite , Imagem Corporal , Feminino , Humanos , Hiperfagia/fisiopatologia , Masculino , Política Nutricional , Sobrepeso/etiologia , Cooperação do Paciente , Estudantes , Estados Unidos , Universidades , Adulto Jovem
17.
MedEdPORTAL ; 20: 11429, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39184363

RESUMO

Introduction: Child abuse pediatrics is an underrepresented area of medical education. To date, the available teaching materials about child abuse in MedEdPORTAL do not address burn injury, and the available materials about burn injury do not address child abuse. We created an interactive, case-based module on abusive pediatric burns to fill this educational gap. Methods: The abusive pediatric burns module was presented to a hybrid audience at a 45-minute emergency medicine grand rounds at Mayo Clinic. Participants completed a pre- and postmodule assessment to measure their confidence and knowledge pertaining to abusive pediatric burns. Results: Fifty-six attendees, from an audience primarily composed of emergency medicine physicians but also including some multidisciplinary individuals, participated in the module. The median confidence level in assessing pediatric burns for abuse showed a modest increase from 4 (interquartile range [IQR]: 2-6) to 6 (IQR: 5-8), and the proportion of participants answering knowledge questions correctly increased for every question: 18% versus 45%, 41% versus 100%, 59% versus 84%, and 72% versus 100%. Qualitative feedback from the audience was favorable. Discussion: This interactive, case-based module about abusive pediatric burns was successfully administered to an audience at emergency medicine grand rounds. Increases in confidence and knowledge were observed, and positive qualitative feedback was received.


Assuntos
Queimaduras , Maus-Tratos Infantis , Currículo , Pediatria , Humanos , Pediatria/educação , Criança , Médicos/psicologia , Competência Clínica/normas , Medicina de Emergência/educação
18.
Arch Dis Child ; 109(4): 321-325, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38290777

RESUMO

OBJECTIVE: The concept of patient-centred care is central to the role of cancer multidisciplinary teams (MDTs) and particularly pertinent with the recent rise in number of virtual national advisory panels (NAPs) for childhood cancer in the UK. We sought to explore patient and caregiver views regarding MDT working and NAPs. METHODS: Three focus groups were undertaken between March 2019 and January 2020. RESULTS: Sixteen participants attended. All regarded MDTs and NAPs highly, while highlighting patient involvement in decision-making should not be diluted by this process. The importance of personalised consultations was stressed, acknowledging that information-sharing preferences may change with circumstance and time. Most participants felt they had not been actively involved in decisions, including those made following MDT or NAP discussions. Group suggestions to improve patient-centred care included a clinician knowing them presenting their case, referral proformas to include family-related factors and an advocate attending meetings to represent the patient/family view. CONCLUSION: Several changes have been driven forward by this work, including the modification of NAP referral proformas to include additional information. Patient and parent perspectives are now embedded into a best practice model for the NAPs to promote personalised recommendations at national level.


Assuntos
Neoplasias , Equipe de Assistência ao Paciente , Criança , Humanos , Neoplasias/terapia , Pesquisa Qualitativa , Grupos Focais , Reino Unido
19.
Geroscience ; 46(6): 5767-5780, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38589671

RESUMO

Reduced insulin/IGF-1 signalling (rIIS) improves survival across diverse taxa and there is a growing interest in its role in regulating immune function. Whilst rIIS can improve anti-bacterial resistance, the consequences for anti-viral immunity are yet to be systematically examined. Here, we show that rIIS in adult Caenorhabditis elegans increases the expression of key genes in two different anti-viral immunity pathways, whilst reducing viral load in old age, increasing survival and reducing rate-of-senescence under infection by naturally occurring positive-sense single-stranded RNA Orsay virus. We found that both drh-1 in the anti-viral RNA interference (RNAi) pathway and cde-1 in the terminal uridylation-based degradation of viral RNA pathway were upregulated in early adulthood under rIIS and increased anti-viral resistance was not associated with reproductive costs. Remarkably, rIIS increased anti-viral gene expression only in infected worms, potentially to curb the costs of constitutively upregulated immunity. RNA viruses are found across taxa from plants to mammals and we demonstrate a novel role for rIIS in regulating resistance to viral infection. We therefore highlight this evolutionarily conserved signalling pathway as a promising therapeutic target to improve anti-viral immunity.


Assuntos
Caenorhabditis elegans , Fator de Crescimento Insulin-Like I , Insulina , Transdução de Sinais , Regulação para Cima , Carga Viral , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/imunologia , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/genética , Insulina/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Interferência de RNA
20.
Mar Environ Res ; 202: 106778, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39378529

RESUMO

Defining and delineating species distribution and habitat is critical to informed management and conservation. This process is complicated in marine environments, where detection of marine taxa and characterization of marine habitat is more difficult. Small pelagic fishes and forage fishes are particularly challenging, though insights may be more accessible in species highly dependent on particular habitat. Pacific sand lance (Ammodytes personatus) is a common and ecologically-important pelagic fish that relies on specific benthic sediments for rest and refuge from predation. We applied multibeam echosounder (MBES) bathymetric data to develop high-definition benthic habitat maps and implemented multiyear sampling to assess potential habitat for sand lance via in situ sampling of sediments. We also applied acoustic Doppler current profilers (ADCP) data and tidally-driven volume-based ocean models to measure current strength and to visualize currents. We leveraged this data to further define and describe habitat for this important forage species. Sediment transport processes were mapped and areas of dispersal, embedment, and accumulation were evaluated. Dynamic bedform habitats, banner banks and glacial banks were identified as potential habitat and sampled for fish presence, density and sediment composition. In the central Salish Sea, approximately 25% of benthic substrates represent potential sand lance habitat. Sand lance prevalence and density correlated with substrate type and sediment coarseness. Densities were highest in areas of coarse grain sediments and presence was limited by fine particulates, such as silt and mud. Tidal currents appear important. Presence and densities of sand lance were correlated with current velocity and distance from current flow path. Nearly all viable sites were located on the immediate margins of high flow (<0.16 km from tidal currents with max speed of 1.72-2.58 m/s). While both flood and ebb were important, processes related to flood were dominant. Viable habitat was not constrained by depth. These results inform a developing atlas for sand lance in the central Salish Sea, provide new insights to subtidal sand lance habitat, characterize conditions that create and maintain subtidal benthic habitat, and provide a template for mapping habitat for this species in the coastal Pacific Ocean.

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