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Many DNA-processing enzymes have been shown to contain a [4Fe4S] cluster, a common redox cofactor in biology. Using DNA electrochemistry, we find that binding of the DNA polyanion promotes a negative shift in [4Fe4S] cluster potential, which corresponds thermodynamically to a â¼500-fold increase in DNA-binding affinity for the oxidized [4Fe4S]3+ cluster versus the reduced [4Fe4S]2+ cluster. This redox switch can be activated from a distance using DNA charge transport (DNA CT) chemistry. DNA-processing proteins containing the [4Fe4S] cluster are enumerated, with possible roles for the redox switch highlighted. A model is described where repair proteins may signal one another using DNA-mediated charge transport as a first step in their search for lesions. The redox switch in eukaryotic DNA primases appears to regulate polymerase handoff, and in DNA polymerase δ, the redox switch provides a means to modulate replication in response to oxidative stress. We thus describe redox signaling interactions of DNA-processing [4Fe4S] enzymes, as well as the most interesting potential players to consider in delineating new DNA-mediated redox signaling networks.
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DNA Glicosilases/química , DNA Helicases/química , DNA Polimerase Dirigida por DNA/química , DNA/química , Endonucleases/química , Genoma , Proteínas Ferro-Enxofre/química , Animais , Bactérias/genética , Bactérias/metabolismo , DNA/metabolismo , DNA/ultraestrutura , Dano ao DNA , DNA Glicosilases/metabolismo , DNA Glicosilases/ultraestrutura , DNA Helicases/metabolismo , DNA Helicases/ultraestrutura , Reparo do DNA , Replicação do DNA , DNA Polimerase Dirigida por DNA/metabolismo , DNA Polimerase Dirigida por DNA/ultraestrutura , Espectroscopia de Ressonância de Spin Eletrônica , Endonucleases/metabolismo , Endonucleases/ultraestrutura , Proteínas Ferro-Enxofre/metabolismo , Proteínas Ferro-Enxofre/ultraestrutura , Oxirredução , Ligação Proteica , Transdução de Sinais , TermodinâmicaRESUMO
A compact protein with a size of <1,000 amino acids, the CRISPR-associated protein CasX is a fundamentally distinct RNA-guided nuclease when compared to Cas9 and Cas12a. Although it can induce RNA-guided genome editing in mammalian cells, the activity of CasX is less robust than that of the widely used S. pyogenes Cas9. Here, we show that structural features of two CasX homologs and their guide RNAs affect the R-loop complex assembly and DNA cleavage activity. Cryo-EM-based structural engineering of either the CasX protein or the guide RNA produced two new CasX genome editors (DpbCasX-R3-v2 and PlmCasX-R1-v2) with significantly improved DNA manipulation efficacy. These results advance both the mechanistic understanding of CasX and its application as a genome-editing tool.
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Edição de Genes , RNA Guia de Cinetoplastídeos , Animais , Sistemas CRISPR-Cas/genética , Endonucleases/genética , Endonucleases/metabolismo , Edição de Genes/métodos , Mamíferos/metabolismo , RNA/genética , RNA Guia de Cinetoplastídeos/genética , RNA Guia de Cinetoplastídeos/metabolismoRESUMO
INTRODUCTION: Absent contractility on high-resolution manometry (HRM) defines severe hypomotility but needs distinction from achalasia. We retrospectively identified achalasia within absent contractility using HRM provocative maneuvers, barium esophagography, and functional lumen imaging probe (FLIP). METHODS: Adult patients with absent contractility on HRM during the 4-year study period were eligible for inclusion. Inadequate studies, achalasia after therapy, or prior foregut surgery were exclusions. Upright integrated relaxation pressure (IRP) >12 mm Hg, panesophageal pressurization, and/or elevated IRP on multiple rapid swallows and rapid drink challenge (RDC) were considered abnormal. Esophageal barium retention and abnormal esophagogastric junction distensibility index (<2.0 mm 2 /mm Hg) on FLIP defined achalasia. Clinical, endoscopic, and motor characteristics of patients with achalasia were compared with absent contractility without obstruction. RESULTS: Of 164 patients, 20 (12.2%) had achalasia (17.9% of 112 patients with adjunctive testing), while 92 did not, and 52 did not undergo adjunctive tests. Achalasia was diagnosed regardless of IRP value, but the median supine IRP was higher (odds ratio 1.196, 95% confidence interval 1.041-1.375, P = 0.012). Patients with achalasia were more likely to present with dysphagia (80.0% vs 35.9%, P < 0.001), with obstructive features on HRM maneuvers (83.3% vs 48.9%, P = 0.039), but lower likelihood of GERD evidence (20.0% vs 47.3%, P = 0.027) or large hiatus hernia (15.0% vs 43.8%, P = 0.002). On multivariable analysis, dysphagia presentation ( P = 0.006) and pressurization on RDC ( P = 0.027) predicted achalasia, while reflux and presurgical evaluations and lack of RDC obstruction predicted absent contractility without obstruction. DISCUSSION: Despite HRM diagnosis of absent contractility, achalasia is identified in more than 1 in 10 patients regardless of IRP value.
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BACKGROUND: Autism spectrum disorder (ASD) is a neurocognitive disorder characterized by impairments in communication and socialization. There are little data comparing the differences in perioperative outcomes in children with and without ASD. We hypothesized that children with ASD would have higher postoperative pain scores than those without ASD. METHODS: Pediatric patients undergoing ambulatory tonsillectomy/adenoidectomy, ophthalmological surgery, general surgery, and urologic procedures between 2016 and 2021 were included in this retrospective cohort study. ASD patients, defined by International Classification of Diseases-9/10 codes, were compared to controls utilizing inverse probability of treatment weighting based on surgical category/duration, age, sex, race and ethnicity, anesthetizing location, American Society of Anesthesiology physical status, intraoperative opioid dose, and intraoperative dexmedetomidine dose. The primary outcome was the maximum postanesthesia care unit (PACU) pain score, and secondary outcomes included premedication administration, behavior at induction, PACU opioid administration, postoperative vomiting, emergence delirium, and PACU length of stay. RESULTS: Three hundred thirty-five children with ASD and 11,551 non-ASD controls were included. Maximum PACU pain scores in the ASD group were not significantly higher than controls (median, 5; interquartile range [IQR], 0-8; ASD versus median, 5; IQR, 0-8 controls; median difference [95% confidence interval {CI}] of 0 [-1.1 to 1.1]; P = .66). There was no significant difference in the use of premedication (96% ASD versus 95% controls; odds ratio [OR], 1.5; [95% CI, 0.9-2.7]; P = .12), but the ASD cohort had significantly higher odds of receiving an intranasal premedication (4.2% ASD versus 1.2% controls; OR, 3.5 [95% CI, 1.8-6.8]; P < .001) and received ketamine significantly more frequently (0.3% ASD versus <0.1% controls; P < .001). Children with ASD were more likely to have parental (4.9% ASD versus 1.0% controls; OR, 5 [95% CI, 2.1-12]; P < .001) and child life specialist (1.3% ASD versus 0.1% controls; OR, 9.9 [95% CI, 2.3-43]; P < .001) presence at induction, but were more likely to have a difficult induction (11% ASD versus 3.4% controls; OR, 3.42 [95% CI, 1.7-6.7]; P < .001). There were no significant differences in postoperative opioid administration, emergence delirium, vomiting, or PACU length of stay between cohorts. CONCLUSIONS: We found no difference in maximum PACU pain scores in children with ASD compared to a similarly weighted cohort without ASD. Children with ASD had higher odds of a difficult induction despite similar rates of premedication administration, and significantly higher parental and child life specialist presence at induction. These findings highlight the need for future research to develop evidence-based interventions to optimize the perioperative care of this population.
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Transtorno do Espectro Autista , Delírio do Despertar , Humanos , Criança , Analgésicos Opioides/efeitos adversos , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/induzido quimicamente , Estudos Retrospectivos , Delírio do Despertar/induzido quimicamente , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controleRESUMO
BACKGROUND: Point-of-care ultrasound is an invaluable bedside tool for anesthesiologists and has been integrated into anesthesiology residency training and board certification in the United States. Little is known about point-of-care ultrasound training practices in pediatric anesthesia fellowship programs. AIMS: To describe the current state of point-of-care ultrasound education in pediatric anesthesia fellowship programs in the United States. METHODS: We conducted a cross-sectional survey study distributed to 60 American Accreditation Council for Graduate Medical Education-accredited pediatric anesthesia fellowship programs. Two programs were in their initial accreditation period and were excluded due to lack of historical data. Program directors or associate program directors were invited to complete this 23-item survey. RESULTS: Thirty-three of fifty-eight programs (57%) completed the survey. Of those, 15 programs (45%) reported having a point-of-care ultrasound curriculum. Programs with ≤3 fellows per year were less likely to have an ultrasound curriculum compared to programs with ≥4 fellows per year (30% programs 0-3 fellows/year vs. 69% programs ≥4 fellows/year, odds ratio 0.19 [95% confidence intervals 0.04-0.87]; p = .03). Program directors and associate program directors rated point-of-care ultrasound training as highly valuable to fellows' education. Barriers to use most commonly included lack of experience (64%), lack of oversight/interpretive guidance (58%), and lack of time (45%). Programs without point-of-care ultrasound training had significantly higher odds of listing lack of ultrasound access as a primary barrier (50% programs without vs. 13% programs with, odds ratio 6.5, [95% confidence intervals 1.3-50]; p = .04). CONCLUSIONS: This observational survey-based study suggests that fewer than half of pediatric anesthesia training programs in the United States offer point-of-care ultrasound education. Additional research is needed to optimize this education and training in pediatric anesthesia fellowship programs.
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Anestesiologia , Bolsas de Estudo , Anestesia Pediátrica , Pediatria , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia , Humanos , Acreditação , Anestesiologia/educação , Estudos Transversais , Currículo , Educação de Pós-Graduação em Medicina/métodos , Internato e Residência , Pediatria/educação , Inquéritos e Questionários , Ultrassonografia/estatística & dados numéricos , Estados UnidosRESUMO
BACKGROUND: Friedreich ataxia is a rare genetic disorder associated with progressive mitochondrial dysfunction leading to widespread sequelae including ataxia, muscle weakness, hypertrophic cardiomyopathy, diabetes mellitus, and neuromuscular scoliosis. Children with Friedreich ataxia are at high risk for periprocedural complications during posterior spinal fusion due to their comorbidities. AIM: To describe our single-center perioperative management of patients with Friedreich ataxia undergoing posterior spinal fusion. METHODS: Adolescent patients with Friedreich ataxia presenting for spinal deformity surgery between 2007 and 2023 were included in this retrospective case series performed at the Children's Hospital of Philadelphia. Perioperative outcomes were reviewed along with preoperative characteristics, intraoperative anesthetic management, and postoperative medical management. RESULTS: Seventeen patients were included in the final analysis. The mean age was 15 ± 2 years old and 47% were female. Preoperatively, 35% were wheelchair dependent, 100% had mild-to-moderate hypertrophic cardiomyopathy with preserved systolic function and no left ventricular outflow tract obstruction, 29% were on cardiac medications, and 29% were on pain medications. Intraoperatively, 53% had transesophageal echocardiography monitoring; 12% had changes in volume status on echo but no changes in function. Numerous combinations of total intravenous anesthetic agents were used, most commonly propofol, remifentanil, and ketamine. Baseline neuromonitoring signals were poor in four patients and one patient lost signals, resulting in 4 (24%) wake-up tests. The majority (75%) were extubated in the operating room. Postoperative complications were high (88%) and ranged from minor complications like nausea/vomiting (18%) to major complications like hypotension/tachycardia (29%) and need for extracorporeal membrane oxygenation support in one patient (6%). CONCLUSIONS: Patients with Friedreich ataxia are at high risk for perioperative complications when undergoing posterior spinal fusion and coordinated multidisciplinary care is required at each stage. Future research should focus on the utility of intraoperative echocardiography, optimal anesthetic agent selection, and targeted fluid management to reduce postoperative cardiac complications.
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Ataxia de Friedreich , Assistência Perioperatória , Fusão Vertebral , Humanos , Feminino , Estudos Retrospectivos , Ataxia de Friedreich/complicações , Fusão Vertebral/métodos , Masculino , Adolescente , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Criança , Escoliose/cirurgiaRESUMO
OBJECTIVES: To determine whether neonatal conjugated or direct bilirubin levels were elevated in infants with biliary atresia (BA) and to estimate the number of newborns who would have positive screens in the nursery necessitating repeat testing after discharge. STUDY DESIGN: We used administrative data from a large integrated healthcare network in Utah to identify newborns who had a fractionated bilirubin recorded during birth admission from 2005 through 2019. Elevated conjugated bilirubin was defined as greater than 0.2 mg/dL and direct bilirubin was defined as greater than 0.5 mg/dL (>97.5th percentile for the assays). We performed simulations to estimate the anticipated number of false-positive screens. RESULTS: There were 32 cases of BA and 468â161 live births during the study period (1/14 700). There were 252â892 newborns with fractionated bilirubin assessed, including 26 of those subsequently confirmed to have BA. Conjugated or direct bilirubin was elevated in all 26 infants with BA and an additional 3246 newborns (1.3%) without BA. Simulated data suggest 9-21 per 1000 screened newborns will have an elevated conjugated or direct bilirubin using laboratory-based thresholds for a positive screen. Screening characteristics improved with higher thresholds without increasing false-negative tests. CONCLUSIONS: This study validates the previous findings that conjugated or direct bilirubin are elevated in the newborn period in patients with BA. A higher threshold for conjugated bilirubin improved screening performance. Future studies are warranted to determine the optimal screening test for BA and to assess the effectiveness and cost-effectiveness of implementing such a program.
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Atresia Biliar , Lactente , Recém-Nascido , Humanos , Atresia Biliar/diagnóstico , Bilirrubina , Estudos de Coortes , Utah/epidemiologia , Testes de Função HepáticaRESUMO
Part 2 of this 2-part CME introduces dermatologists to noninfectious inflammatory skin diseases associated with pulmonary involvement. In many cases, dermatologists may be the first physicians recognizing respiratory complications associated with these diagnoses. Because pulmonary involvement is often the leading cause of morbidity and mortality, dermatologists should be comfortable screening and monitoring for lung disease in high-risk patients, recognizing cutaneous stigmata of lung disease in these patients and referring to pulmonary specialists, when appropriate, for prompt treatment initiation. Some treatments used for skin disease may not be appropriate in the context of lung disease and hence, choosing a holistic approach is important. Interstitial lung disease and pulmonary hypertension are the most common pulmonary complications and a significant cause of mortality in autoimmune connective tissue diseases, especially systemic sclerosis, dermatomyositis, and mixed connective tissue disease. Pulmonary complications, notably interstitial lung disease, are also common and life-threatening in sarcoidosis and vasculitis, while they are variable in neutrophilic and autoimmune blistering diseases.
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Doenças Autoimunes , Doenças do Tecido Conjuntivo , Doenças Pulmonares Intersticiais , Dermatopatias , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Doenças do Tecido Conjuntivo/complicações , Pulmão , Doenças Autoimunes/complicações , Dermatopatias/complicações , Dermatopatias/diagnósticoRESUMO
BACKGROUND: Sex and gender have increasingly been recognized as significant risk factors for many diseases, including dermatological conditions. Historically, sex and gender have often been grouped together as a single risk factor in the scientific literature. However, both may have a distinct impact on disease incidence, prevalence, clinical presentation, severity, therapeutic response, and associated psychological distress. OBJECTIVES AND PROJECT DESCRIPTION: The mechanisms that underlie differences in skin diseases between males, females, men, and women remain largely unknown. The specific objectives of this review paper are:To highlight the biological differences between males and females (sex), as well as the sociocultural differences between men and women (gender) and how they impact the integumentary system.To perform a literature review to identify important sex- and gender-related epidemiological and clinical differences for various skin conditions belonging to a range of disease categories and to discuss possible biological and sociocultural factors that could explain the observed differences.To discuss dermatological skin conditions and gender-affirming treatments within the transgender community, a population of individuals who have a gender identity which is different than the gender identity they were assigned at birth. FUTURE IMPACT: With the rising number of individuals that identify as non-binary or transgender within our increasingly diverse communities, it is imperative to recognize gender identity, gender, and sex as distinct entities. By doing so, clinicians will be able to better risk-stratify their patients and select treatments that are most aligned with their values. To our knowledge, very few studies have separated sex and gender as two distinct risk factors within the dermatology literature. Our article also has the potential to help guide future prevention strategies that are patient-tailored rather than using a universal approach.
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Dermatologia , Pessoas Transgênero , Recém-Nascido , Humanos , Masculino , Feminino , Identidade de Gênero , Pessoas Transgênero/psicologia , Fatores de RiscoRESUMO
Advances in ultrasound technology and non-surgical treatments of basal cell carcinomas (BCCs) have raised the need to study the performance of high-frequency ultrasound (HFUS) in BCCs. We aimed to assess the performance of HFUS in the evaluation of BCCs to formulate recommendations for its uses and conducted a systematic review of the literature to do so. A search of Central, Medline, Embase, CINHAL, and Web of Science was performed using key/MESH terms "ultrasonography" and "basal cell carcinoma" (January 2005-December 2020). We included primary studies reporting biopsy-confirmed BCCs for which the target intervention was ultrasound assessment at 15 MHz or higher frequency. Thirty articles were included, studying a total of 1,203 biopsy-confirmed BCCs. HFUS provides accurate depth measurements, especially for BCCs >1 mm. The definition of lateral margins in vivo needs further studies; however, ex vivo margin assessment seems convincing. There is a diagnostic role for HFUS in identifying higher recurrence risk BCC subtypes, which can help in risk stratification. Performance of HFUS is significant in BCC management. Pre-surgical scans may support case selection for Mohs. HFUS can improve safety when used to plan brachytherapy treatments, help with case selection and adjunct treatment choice pre-photodynamic therapy. Finally, HFUS can help follow lesions after intervention, particularly non-surgical management, and support the decision to observe or re-intervene. HFUS can enhance clinical practice by providing useful information that cannot be deducted from the clinical examination. It would be recommended to evaluate the extent, mainly depth, and detect the aggressiveness of the BCCs.
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Carcinoma Basocelular , Neoplasias Cutâneas , Biópsia , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/terapia , Humanos , Exame Físico , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/terapia , UltrassonografiaRESUMO
Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease that is characterized by the formation of comedones, papules, nodules, abscesses and sinus tracts in the axillary, inframammary, groin, and gluteal areas. Up to 3.8% of the Canadian population has HS, though due to a lack of awareness of HS, many patients are initially misdiagnosed and do not receive adequate treatment early on in the disease course. Once a diagnosis of HS is made, developing an effective management plan can be a dilemma for many providers. There is significant variability in response to any given therapy within the HS patient population and many HS patients have other medical comorbidities which must be taken into consideration. The aim of this review is to provide a practical approach for all healthcare providers to diagnose and manage HS and its associated comorbidities. A sample electronic medical record template for HS management was developed by the Canadian Hidradenitis Suppurativa Foundation Executive Board and is intended for use in clinical settings. This will help to increase collaboration between primary healthcare providers, dermatologists, and other medical specialists and ultimately improve the quality of care that HS patients receive.
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Hidradenite Supurativa , Guias de Prática Clínica como Assunto , Canadá/epidemiologia , Comorbidade , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/epidemiologia , Hidradenite Supurativa/terapia , HumanosRESUMO
In order to reduce iron deficiency in neonates at-risk for iron deficiency, we implemented a guideline to increase the consistency of early iron supplementation in infants of diabetic mothers, small for gestational age neonates and very low birthweight premature neonates. Three years following implementation we performed a retrospective analysis in order to assess adherence to the guideline and to compare timing of early iron supplementation and reticulocyte-hemoglobin (RET-He) values at one month of life in at-risk infants. Adherence with early iron supplementation guidelines was 73.4% (399/543) with 51% (275/543) having RET-He values obtained at one month. Despite good adherence, 16% (44/275) had RET-He <25 pg (5th percentile for gestational age). No infants receiving red blood cell transfusion (0/20) had RET-He <25 pg vs. 26.1% (40/153) of those treated with darbepoetin (p < 0.001). There was no evidence of increased feeding intolerance (episodes of emesis/day) with early iron supplementation.
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Unidades de Terapia Intensiva Neonatal , Deficiências de Ferro/tratamento farmacológico , Ferro/administração & dosagem , Feminino , Humanos , Recém-Nascido , Ferro/efeitos adversos , Deficiências de Ferro/sangue , Masculino , Estudos RetrospectivosRESUMO
Eukaryotic DNA primases contain a [4Fe4S] cluster in the C-terminal domain of the p58 subunit (p58C) that affects substrate affinity but is not required for catalysis. We show that, in yeast primase, the cluster serves as a DNA-mediated redox switch governing DNA binding, just as in human primase. Despite a different structural arrangement of tyrosines to facilitate electron transfer between the DNA substrate and [4Fe4S] cluster, in yeast, mutation of tyrosines Y395 and Y397 alters the same electron transfer chemistry and redox switch. Mutation of conserved tyrosine 395 diminishes the extent of p58C participation in normal redox-switching reactions, whereas mutation of conserved tyrosine 397 causes oxidative cluster degradation to the [3Fe4S]+ species during p58C redox signaling. Switching between oxidized and reduced states in the presence of the Y397 mutations thus puts primase [4Fe4S] cluster integrity and function at risk. Consistent with these observations, we find that yeast tolerate mutations to Y395 in p58C, but the single-residue mutation Y397L in p58C is lethal. Our data thus show that a constellation of tyrosines for protein-DNA electron transfer mediates the redox switch in eukaryotic primases and is required for primase function in vivo.
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DNA Primase/química , Proteínas Ferro-Enxofre/química , Proteínas de Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/enzimologia , Cristalografia por Raios X , DNA Primase/genética , Transporte de Elétrons , Proteínas Ferro-Enxofre/genética , Modelos Moleculares , Mutação , Oxirredução , Conformação Proteica , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
BACKGROUND: The traditional concept that heritability occurs exclusively from the transfer of germline-restricted genetics is being challenged by the increasing accumulation of evidence confirming the existence of experience-dependent transgenerational inheritance. However, questions remain unanswered as to how heritable information can be passed from somatic cells. Previous studies have implicated the critical involvement of RNA in heritable transgenerational effects, and the high degree of mobility and genomic impact of RNAs in all organisms is an attractive model for the efficient transfer of genetic information. RESULTS: We hypothesized that RNA may be transported from a somatic tissue, in this case the brain, of an adult male mouse to the germline, and subsequently to embryos. To investigate this, we injected one hemisphere of the male mouse striatum with an AAV1/9 virus expressing human pre-MIR941 (MIR941). After 2, 8 and 16 weeks following injection, we used an LNA-based qPCR system to detect the presence of virus and human MIR941 in brain, peripheral tissues and embryos, from injected male mice mated with uninjected females. Virus was never detected outside of the brain. Verification of single bands of the correct size for MIR941 was performed using Sanger sequencing while quantitation demonstrated that a small percentage (~ 1-8%) of MIR941 is transported to the germline and to embryos in about a third of the cases. CONCLUSIONS: We show that somatic RNA can be transported to the germline and passed on to embryos, thereby providing additional evidence of a role for RNA in somatic cell-derived intergenerational effects.
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Encéfalo/fisiologia , Epigênese Genética , Células Germinativas/metabolismo , Padrões de Herança , MicroRNAs/metabolismo , Transporte de RNA , Animais , Hereditariedade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/administração & dosagemRESUMO
OBJECTIVES: When obtaining informed permission from parents for invasive procedures, trainees and supervisors often do not disclose information about the trainee's level of experience. The objectives of this study were 3-fold: (1) to assess parents' understanding of both academic medical training and the role of the trainee and the supervisor, (2) to explore parents' preferences about transparency related to a trainee's experience, and (3) to examine parents' willingness to allow trainees to perform invasive procedures. METHODS: This qualitative study involved 23 one-on-one interviews with parents of infants younger than 30 days who had undergone a lumbar puncture. In line with grounded theory, researchers independently coded transcripts and then collectively refined codes and created themes. Data collection and analysis continued until thematic saturation was achieved. In addition, to triangulate the findings, a focus group was conducted with Yale School of Medicine's Community Bioethics Forum. RESULTS: Our analysis revealed 4 primary themes: (1) the invasive nature of a lumbar puncture and the vulnerability of the newborn creates fear in parents, which may be mitigated by improved communication; (2) parents have varying degrees of awareness of the medical training system; (3) most parents expect transparency about provider experience level and trust that a qualified provider will be performing the procedure; and (4) parents prefer an experienced provider to perform a procedure, but supervisor presence may be a qualifying factor for inexperienced providers. CONCLUSIONS: Physicians must find a way to improve transparency when caring for pediatric patients while still developing critical procedural skills.
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Atitude Frente a Saúde , Educação de Pós-Graduação em Medicina , Pais/psicologia , Medicina de Emergência Pediátrica/educação , Punção Espinal/métodos , Adulto , Competência Clínica , Comunicação , Serviço Hospitalar de Emergência , Medo , Feminino , Grupos Focais , Humanos , Recém-Nascido , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Medicina de Emergência Pediátrica/organização & administração , Pesquisa Qualitativa , Confiança , Adulto JovemRESUMO
Parents are key to children's health because they can influence children's eating behavior and body image and can make health-related decisions for children. Despite their influence, research on parents' opinions about parenting practices related to weight and eating is limited. Experimental vignettes examined parents' perceptions of parent-child interactions around body image, eating, and weight loss. We manipulated vignette-child weight (healthy-weight, overweight) and communication tone (positive, negative, neutral) to assess their influence on parents' perceptions. Parents (N = 233, 27.5% fathers, 72.5% mothers) were randomly assigned to read one of six vignettes. When the vignette-child had overweight, parents were more likely to recommend seeking help for body image and that the vignette-parent should choose the restaurant food order. Parents were less opposed to commenting on the vignette-child's weight when tone was positive. Parents were more likely to recommend weight-loss efforts that could be implemented by the family rather than those requiring professional assistance. This study is among the first to examine parents' opinions about parenting practices related to weight and eating using an experimental design. Findings might inform future research and continued work on prevention and treatment applications to help align parents' existing opinions about weight and eating with evidence-based health-promoting strategies.
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Imagem Corporal/psicologia , Peso Corporal , Comportamento Infantil/psicologia , Comportamento Alimentar/psicologia , Relações Pais-Filho , Poder Familiar/psicologia , Percepção Social , Adulto , Criança , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Humans have adapted to widespread changes during the past 2 million years in both environmental and lifestyle factors. This is evident in overall body alterations such as average height and brain size. Although we can appreciate the uniqueness of our species in many aspects, molecular variations that drive such changes are far from being fully known and explained. Comparative genomics is able to determine variations in genomic sequence that may provide functional information to better understand species-specific adaptations. A large number of human-specific genomic variations have been reported but no currently available dataset comprises all of these, a problem which contributes to hinder progress in the field. RESULTS: Here we critically update high confidence human-specific genomic variants that mostly associate with protein-coding regions and find 856 related genes. Events that create such human-specificity are mainly gene duplications, the emergence of novel gene regions and sequence and structural alterations. Functional analysis of these human-specific genes identifies adaptations to brain, immune and metabolic systems to be highly involved. We further show that many of these genes may be functionally associated with neural activity and generating the expanded human cortex in dynamic spatial and temporal contexts. CONCLUSIONS: This comprehensive study contributes to the current knowledge by considerably updating the number of human-specific genes following a critical bibliographic survey. Human-specific genes were functionally assessed for the first time to such extent, thus providing unique information. Our results are consistent with environmental changes, such as immune challenges and alterations in diet, as well as neural sophistication, as significant contributors to recent human evolution.
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Evolução Biológica , Encéfalo/imunologia , Encéfalo/metabolismo , Genes , Animais , Bases de Dados Genéticas , Ontologia Genética , Genoma Humano , Genômica , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Especificidade da EspécieRESUMO
BACKGROUND: An emergency-release blood transfusion (ERBT) protocol (uncrossmatched type O-negative red blood cells, AB plasma, AB platelets) is critical for neonatology practice. However, few reports of emergency transfusions are available. We conducted an ERBT quality improvement project as a basis for progress. STUDY DESIGN AND METHODS: For each ERBT in the past 8 years, we logged indications, products, locations and timing of the transfusions, and outcomes. RESULTS: One hundred forty-nine ERBTs were administered; 42% involved a single blood product, and 58% involved two or more. The incidence was 6.25 ERBT per 10,000 live births, with a higher rate (9.52 ERBT/10,000) in hospitals with a Level 3 neonatal intensive care unit (NICU) (p < 0.001). Seventy percent of ERBTs were administered in a NICU and 30% in a delivery room, operating room, or emergency department. Indications were abruption/previa (32.2%), congenital anemia (i.e., fetomaternal hemorrhage; 15.4%), umbilical cord accident (i.e., velamentous insertion; 15.0%), and bleeding/coagulopathy (12.8%). Fifty-eight percent of those with hemorrhage before birth did not have a hemoglobin value reported on the umbilical cord gas; thus, anemia was not recognized initially. None of the 149 ERBTs were administered using a blood warmer. The mortality rate of recipients was 35%. CONCLUSION: Based on our findings, we recommend including a hemoglobin value with every cord blood gas after emergency delivery to rapidly identify fetal anemia. We also discuss two potential improvements for future testing: 1) the use of a warming device for massive transfusion of neonates and 2) the use of low-titer group O cold-stored whole blood for massive hemorrhage in neonates.
Assuntos
Anemia , Transfusão de Sangue , Serviços Médicos de Emergência , Transfusão Feto-Materna , Anemia/sangue , Anemia/terapia , Feminino , Transfusão Feto-Materna/sangue , Transfusão Feto-Materna/terapia , Humanos , Lactente , Recém-Nascido , Masculino , GravidezRESUMO
BACKGROUND: In cases of massive hemorrhage in the US military, improved outcomes have been reported with the use of warm, fresh whole blood transfusions. Cold-stored low-titer type O whole blood (LTOWB) has become the preferred product for resuscitation of severe bleeding in deployed surgical units. Reports of LTOWB use in civilian trauma are becoming more frequent. CASE REPORT: We report our experience with emergency transfusion of LTOWB for a woman with massive postpartum hemorrhage. The patient had two previous cesarean section deliveries at term without complications. With her third elective cesarean section at term, blood loss during surgery was not excessive, but 3 to 4 hours later she had an estimated blood loss of 3600 mL. Despite measures to control the hemorrhage, she rapidly became hypotensive and tachycardic, and our massive transfusion protocol (MTP) was activated. The transfusion service had very recently incorporated LTOWB into Trauma Pack 1 of the MTP. She received two LTOWB units, after which her hemorrhaging ceased, blood pressure normalized, and she became alert. One hour later she received one unit of fresh frozen plasma and one unit of red blood cells (RBCs). The following morning she received one unit of crossmatched RBCs, for a hematocrit of 20.7%. She was discharged home on Day 4, and she remains healthy. CONCLUSIONS: This is the first report of which we are aware of massive postpartum hemorrhage treated using LTOWB. Our positive experience leads us to speculate that this approach could have a role in massive obstetric hemorrhage.
Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Preservação de Sangue , Transfusão de Sangue , Hemorragia Pós-Parto/terapia , Ressuscitação , Adulto , Feminino , Humanos , Hemorragia Pós-Parto/sangue , Gravidez , Índice de Gravidade de DoençaRESUMO
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder. A genetic component in the pathogenesis is highly likely considering that ~30% to 40% of patients with HS report a family history of the disease. The genetic mutations related to HS that have been reported to date suggest HS can be inherited as a monogenic trait because of a defect in either the Notch signaling pathway or inflammasome function, or as a polygenic disorder resulting from defects in genes regulating epidermal proliferation, ceramide production, or in immune system function. This review provides a summary of genetic mutations reported in patients diagnosed with HS and discusses the mechanisms by which these genes are involved in its pathogenesis.