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An effective vaccine is needed for the prevention and elimination of malaria. The only immunogens that have been shown to have a protective efficacy of more than 90% against human malaria are Plasmodium falciparum (Pf) sporozoites (PfSPZ) manufactured in mosquitoes (mPfSPZ)1-7. The ability to produce PfSPZ in vitro (iPfSPZ) without mosquitoes would substantially enhance the production of PfSPZ vaccines and mosquito-stage malaria research, but this ability is lacking. Here we report the production of hundreds of millions of iPfSPZ. iPfSPZ invaded human hepatocytes in culture and developed to mature liver-stage schizonts expressing P. falciparum merozoite surface protein 1 (PfMSP1) in numbers comparable to mPfSPZ. When injected into FRGhuHep mice containing humanized livers, iPfSPZ invaded the human hepatocytes and developed to PfMSP1-expressing late liver stage parasites at 45% the quantity of cryopreserved mPfSPZ. Human blood from FRGhuHep mice infected with iPfSPZ produced asexual and sexual erythrocytic-stage parasites in culture, and gametocytes developed to PfSPZ when fed to mosquitoes, completing the P. falciparum life cycle from infectious gametocyte to infectious gametocyte without mosquitoes or primates.
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Plasmodium falciparum , Esporozoítos , Animais , Humanos , Camundongos , Culicidae/parasitologia , Malária/parasitologia , Malária/prevenção & controle , Vacinas Antimaláricas/biossíntese , Vacinas Antimaláricas/química , Malária Falciparum/parasitologia , Plasmodium falciparum/crescimento & desenvolvimento , Esporozoítos/crescimento & desenvolvimento , Esporozoítos/patogenicidade , Hepatócitos/parasitologia , Fígado/parasitologia , Proteína 1 de Superfície de Merozoito , Eritrócitos/parasitologia , Técnicas In VitroRESUMO
Neurons of the peripheral nervous system (PNS) are tasked with diverse roles, from encoding touch, pain, and itch to interoceptive control of inflammation and organ physiology. Thus, technologies that allow precise control of peripheral nerve activity have the potential to regulate a wide range of biological processes. Noninvasive modulation of neuronal activity is an important translational application of focused ultrasound (FUS). Recent studies have identified effective strategies to modulate brain circuits; however, reliable parameters to control the activity of the PNS are lacking. To develop robust noninvasive technologies for peripheral nerve modulation, we employed targeted FUS stimulation and electrophysiology in mouse ex vivo skin-saphenous nerve preparations to record the activity of individual mechanosensory neurons. Parameter space exploration showed that stimulating neuronal receptive fields with high-intensity, millisecond FUS pulses reliably and repeatedly evoked one-to-one action potentials in all peripheral neurons recorded. Interestingly, when neurons were classified based on neurophysiological properties, we identified a discrete range of FUS parameters capable of exciting all neuronal classes, including myelinated A fibers and unmyelinated C fibers. Peripheral neurons were excited by FUS stimulation targeted to either cutaneous receptive fields or peripheral nerves, a key finding that increases the therapeutic range of FUS-based peripheral neuromodulation. FUS elicited action potentials with millisecond latencies compared with electrical stimulation, suggesting ion channelmediated mechanisms. Indeed, FUS thresholds were elevated in neurons lacking the mechanically gated channel PIEZO2. Together, these results demonstrate that transcutaneous FUS drives peripheral nerve activity by engaging intrinsic mechanotransduction mechanisms in neurons [B. U. Hoffman, PhD thesis, (2019)].
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Canais Iônicos , Neurônios , Sistema Nervoso Periférico , Estimulação Elétrica Nervosa Transcutânea , Potenciais de Ação , Animais , Interneurônios , Mamíferos , Neurônios/fisiologia , Sistema Nervoso Periférico/fisiologia , Ultrassonografia/métodosRESUMO
CBL0137 is a lead drug for human African trypanosomiasis, caused by Trypanosoma brucei Herein, we use a four-step strategy to 1) identify physiologic targets and 2) determine modes of molecular action of CBL0137 in the trypanosome. First, we identified fourteen CBL0137-binding proteins using affinity chromatography. Second, we developed hypotheses of molecular modes of action, using predicted functions of CBL0137-binding proteins as guides. Third, we documented effects of CBL0137 on molecular pathways in the trypanosome. Fourth, we identified physiologic targets of the drug by knocking down genes encoding CBL0137-binding proteins and comparing their molecular effects to those obtained when trypanosomes were treated with CBL0137. CBL0137-binding proteins included glycolysis enzymes (aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphofructokinase, phosphoglycerate kinase) and DNA-binding proteins [universal minicircle sequence binding protein 2, replication protein A1 (RPA1), replication protein A2 (RPA2)]. In chemical biology studies, CBL0137 did not reduce ATP level in the trypanosome, ruling out glycolysis enzymes as crucial targets for the drug. Thus, many CBL0137-binding proteins are not physiologic targets of the drug. CBL0137 inhibited 1) nucleus mitosis, 2) nuclear DNA replication, and 3) polypeptide synthesis as the first carbazole inhibitor of eukaryote translation. RNA interference (RNAi) against RPA1 inhibited both DNA synthesis and mitosis, whereas RPA2 knockdown inhibited mitosis, consistent with both proteins being physiologic targets of CBL0137. Principles used here to distinguish drug-binding proteins from physiologic targets of CBL0137 can be deployed with different drugs in other biologic systems. SIGNIFICANCE STATEMENT: To distinguish drug-binding proteins from physiologic targets in the African trypanosome, we devised and executed a multidisciplinary approach involving biochemical, genetic, cell, and chemical biology experiments. The strategy we employed can be used for drugs in other biological systems.
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Trypanosoma brucei brucei , Tripanossomíase Africana , Animais , Humanos , Tripanossomíase Africana/tratamento farmacológico , Tripanossomíase Africana/metabolismo , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/metabolismo , Carbazóis/farmacologia , Desenvolvimento de MedicamentosRESUMO
INTRODUCTION: Since 2001, device-assisted enteroscopy (DAE) has revolutionized the diagnostic and therapeutic capabilities for managing small bowel pathology. Though commonly performed, there have been no recent large studies to assess the use, yield, and risks of DAE and none that include all 3 DAE modalities. We hypothesized that DAE is safe with high diagnostic and therapeutic yields achieved within reasonable procedure duration and here we present a large retrospective multicenter US study evaluating the use, yield, and complications of DAE. METHODS: After obtaining institutional review board approval, electronic records were used to identify all DAE's performed for luminal small bowel evaluation in adult patients at 4 US referral centers (Duke University Medical Center, New York University Langone Medical Center, Louisiana State University Health Sciences Center, and University of Massachusetts Medical Center) from January 1, 2014 to January 1, 2019. Electronic medical records were reviewed to collect and analyze a variety of procedure-related outcomes. Using the data pooled across centers, descriptive statistics were generated for the patient and procedure-related characteristics and outcomes; relationships between characteristics and outcomes were explored. RESULTS: A total of 1787 DAE's were performed over this 5-year period (392 at Duke University Medical Center, 887 at Louisiana State University Health Sciences Center, 312 at New York University Langone Medical Center, and 195 at University of Massachusetts Medical Center). Of these, there were 1017 (57%) double-balloon, 391 (29%) single-balloon, and 378 (21%) spiral enteroscopies. The mean age of patients undergoing DAE was 66 years and 53% of examinations were performed on women; 18% of patients in the cohort underwent >1 DAE over this time span. A total of 53% of examinations were performed for suspected small bowel bleeding, 31% were directly guided by video capsule endoscopy findings and 8% were performed for abnormal imaging. A total of 85% of examinations used an antegrade approach and DAE took a mean of 45 minutes to complete; 76% of examinations revealed abnormal findings, with vascular, inflammatory, and neoplastic findings seen in 49%, 17%, and 15% of the cohort, respectively. Older age was significantly associated with any abnormal finding, including arteriovenous malformations (P<0.0001); 50% of examinations included a therapeutic maneuver, most commonly argon plasma coagulation/cautery (43%). There were complications in 16 examinations (0.9%) including 2 perforations (0.1%), 6 cases with bleeding (0.3%) and 1 episode of pancreatitis (0.1%). CONCLUSIONS: DAE is most commonly performed to evaluate suspected small bowel bleeding and is commonly directed by video capsule findings. DAE is safe, has a high diagnostic yield, with 76% of examinations showing abnormal findings, and frequently features therapeutic maneuvers. Advancing age is associated with abnormal findings on DAE.
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Endoscopia por Cápsula , Enteropatias , Adulto , Idoso , Enteroscopia de Duplo Balão , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos , Enteropatias/diagnóstico , Intestino Delgado/diagnóstico por imagem , Estudos Retrospectivos , Estados UnidosRESUMO
BACKGROUND: Cerebral edema and loss of gray-white matter differentiation on head computed tomography (CT) after cardiac arrest generally portend a poor prognosis. The interobserver variability in physician recognition of hypoxic-ischemic brain injury (HIBI) on early CT after out-of-hospital cardiac arrest has not been studied. METHODS: In this survey study, participating physicians and a neuroradiologist reviewed 20 randomly selected head CTs obtained within 2 h of out-of-hospital cardiac arrest and decided if HIBI was present. All participants were blinded to clinical details. Interobserver agreement on the presence of HIBI (primary outcome) and pairwise agreement between participants and the neuroradiologist (secondary outcome) were determined using multi- and dual-rater kappa statistics with 95% confidence intervals (CIs). RESULTS: Agreement among physicians regarding the presence of HIBI on head CT was fair (kappa 0.34; 95% CI 0.19-0.49). Individual physician agreement with the neuroradiologist varied from poor to moderate (kappa 0.0-0.48), with 8 of 10 physicians having no more than fair agreement. Regarding the perceived severity of HIBI on head CT, physician agreement was moderate (ICC = 0.56; 95% CI 0.38-0.77). CONCLUSION: Physicians, including radiologists, demonstrated substantial interobserver variability when identifying HIBI on head CT soon after out-of-hospital cardiac arrest.
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Lesões Encefálicas , Hipóxia-Isquemia Encefálica , Parada Cardíaca Extra-Hospitalar , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Variações Dependentes do Observador , Parada Cardíaca Extra-Hospitalar/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Distinct firing properties among touch receptors are influenced by multiple, interworking anatomical structures. Our understanding of the functions and crosstalk of Merkel cells and their associated neurites-the end organs of slowly adapting type I (SAI) afferents-remains incomplete. Piezo2 mechanically activated channels are required both in Merkel cells and in sensory neurons for canonical SAI responses in rodents; however, a central unanswered question is how rapidly inactivating currents give rise to sustained action potential volleys in SAI afferents. The computational model herein synthesizes mechanotransduction currents originating from Merkel cells and neurites, in context of skin mechanics and neural dynamics. Its goal is to mimic distinct spike firing patterns from wildtype animals, as well as Atoh1 knockout animals that completely lack Merkel cells. The developed generator function includes a Merkel cell mechanism that represents its mechanotransduction currents and downstream voltage-activated conductances (slower decay of current) and a neurite mechanism that represents its mechanotransduction currents (faster decay of current). To mimic sustained firing in wildtype animals, a longer time constant was needed than the 200 ms observed for mechanically activated membrane depolarizations in rodent Merkel cells. One mechanism that suffices is to introduce an ultra-slowly inactivating current, with a time constant on the order of 1.7 s. This mechanism may drive the slow adaptation of the sustained response, for which the skin's viscoelastic relaxation cannot account. Positioned within the sensory neuron, this source of current reconciles the physiology and anatomical characteristics of Atoh1 knockout animals.
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Células de Merkel/fisiologia , Potenciais de Ação , Biologia Computacional/métodos , Simulação por Computador , Mecanorreceptores/fisiologia , Mecanotransdução Celular/fisiologia , Neuritos/fisiologia , Neurônios Aferentes/fisiologia , Células Receptoras Sensoriais , Pele , Tato/fisiologiaRESUMO
BACKGROUND: Community paediatricians' knowledge of appropriate child safety seat (CSS) use in vehicles may be inadequate. We compared the effectiveness of hands-on and online education in improving and retaining child passenger safety (CPS) knowledge and skills among paediatric trainees. METHODS: Paediatric trainees were randomised to receive hands-on skills training versus a 1-hour online module in CPS. CSS knowledge and installation skills were assessed using a validated 10-item/point questionnaire and an assessment tool respectively at baseline and after 6 months. Preintervention and postintervention knowledge improvement and CSS installation skills between groups were assessed using paired t-tests and effect size (d). RESULTS: Forty-eight students agreed to participate and were randomised. Thirty-nine completed training (hands-on: 23 and online: 15). At entry, no significant differences in learners' demographics and prior CPS education existed. Baseline CPS knowledge scores did not differ significantly between groups (p=0.26). Postintervention, both groups demonstrated a significant increase in knowledge scores (hands-on=3.1 (95% CI 2.4 to 3.7), p<0.0001; online=2.6 (95% CI 1.9 to 3.3), p<0.0001), though the pre-post gain in knowledge scores were not significantly different between groups (p=0.35). At follow-up, both groups demonstrated a significant increase in knowledge scores (hands-on=1.8 (95% CI 1.2 to 2.4), p<0.0001; online=1.1 (95% CI 0.7 to 1.6), p<0.0001) with the hands-on group scores significantly better than the online group (p<0.02). The long-term gain in knowledge scores was not significantly different between groups (p=0.12).Baseline CSS installation skill scores did not significantly differ between groups for forward-facing seats (p=0.16) and rear-facing seats (p=0.51). At follow-up, mean CSS installation skill scores significantly increased for the hands-on group (forward-facing seat: 0.8 (95% CI 0.16 to 1.44), p<0.02; rear-facing seat: 1.2 (95% CI 0.6 to 1.7), p<0.001) but not for the online group (forward-facing seat: 0.9 (95% CI -0.08 to 1.9), p=0.07); rear-facing seat: -0.2 (95% CI -1.1 to 0.7), p=0.6). CONCLUSIONS: Among paediatric trainees, hands-on and online CPS education are both effective in improving long-term CPS knowledge. Long-term installation skills for forward-facing and rear-facing CSS persist for hands-on education but are inconclusive for online education.
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Sistemas de Proteção para Crianças , Conhecimentos, Atitudes e Prática em Saúde , Equipamentos para Lactente , Pediatras/educação , Segurança , Cintos de Segurança , Criança , Pré-Escolar , Humanos , Lactente , Avaliação de Programas e Projetos de Saúde , Estudos ProspectivosRESUMO
We perform the transient absorption spectroscopy experiments to investigate the dynamics of the low-energy collective electron-hole excitations in α-copper phthalocyanine thin films. The results are interpreted in terms of the third-order nonlinear polarization response function. It is found that, initially excited in the molecular plane, the intramolecular Frenkel exciton polarization reorients with time to align along the molecular chain direction to form coupled Frenkel-charge-transfer exciton states, the eigenstates of the one-dimensional periodic molecular lattice. The process pinpoints the direction of the charge separation in α-copper phthalocyanine and similar organic molecular structures. Being able to observe and monitor such processes is important both for understanding the physical principles of organic thin film solar energy conversion device operation and for the development of organic optoelectronics in general.
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BACKGROUND AND PURPOSE: Genes associated with the inflammatory response and cytostructural integrity may influence recovery following a brain injury. To examine this in the setting of spontaneous intracerebral hemorrhage (ICH), selected single nucleotide polymorphisms (SNPs) were assessed for associations with patient outcome. METHODS: A cohort of 54 patients with supratentorial ICH were enrolled. Based on known involvement with neuroinflammation and cytostructural integrity, 10 preselected SNPs from 6 candidate genes were tested for associations with 6-month functional outcome (modified Rankin Scale [mRS] ≥ 3), mortality, and in-hospital deterioration (Glasgow Coma Scale decrease by >2 within 7 days of admission) following ICH. Fisher's exact test and logistic regression with adjustment for race and ICH score were performed. RESULTS: SNP rs10940495 (gp130 G/A) within the gp130 gene was the only SNP significantly associated with lower odds of an unfavorable 6-month functional outcome (odds ratio = .16 for mRS ≥ 3; 95% confidence interval, .03-.87, P = .03). Compared with major allele (A) homozygotes, minor allele (G) carriers in the IL6 signal transducer gene (gp130) locus were 84% less likely to have a poor outcome (mRS ≥ 3) at 6 months following spontaneous ICH. The SNP rs10940495 (gp130 G/A) and SNP rs3219119 (PARP-1 A/T) were associated with 6-month mortality (P = .02 and .04, respectively) only on univariate analysis. None of the SNPs examined were associated with in-hospital deterioration. CONCLUSION: In this exploratory study, SNP rs10940495 in the gp130 locus was associated with functional outcome at 6 months following spontaneous ICH. These findings, which should be validated through a larger study, suggest that inflammation plays an important role in mediating outcomes after ICH.
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Hemorragia Cerebral/genética , Receptor gp130 de Citocina/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/fisiopatologia , Distribuição de Qui-Quadrado , Avaliação da Deficiência , Progressão da Doença , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Escala de Coma de Glasgow , Nível de Saúde , Heterozigoto , Homozigoto , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Prognóstico , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: To examine the prevalence and potential determinants of rear-facing car safety seat use among children approximately 18 months of age born at a university hospital. STUDY DESIGN: We administered a telephone survey to caregivers of children 17-19 months of age who were born between November 2013 and May 2014. The survey was designed to assess the prevalence of rear-facing car safety seat use and estimate the likelihood of rear-facing car safety seat use, compared with forward-facing car seat use, in reference to hypothesized determinants. aORs and 95% CIs were calculated using multivariable logistic regression. RESULTS: In total, 56% of potentially eligible caregivers (491/877) completed the survey; 62% of these reported rear-facing car safety seat use. Race, education, rurality, and household income were associated with rear-facing car safety seat use after controlling for potential confounders. Additionally, caregivers who reported having discussed car seats with their child's provider (aOR 1.7; 95% CI 1.1-2.6); receiving their child's primary care in pediatrics compared with family practice clinics (aOR 2.4; 95% CI 1.1-2.6); and being aware of the American Academy of Pediatrics rear-facing recommendation (aOR 2.8; 95% CI 1.8-4.1) were significantly more likely to report rear-facing car safety seat use. Conversely, caregivers who previously used a car seat with another child were less likely to have their child rear facing at 18 months of age (aOR 0.6; 95% CI 0.4-0.9). CONCLUSIONS: A large proportion of children were forward facing at 18 months of age. Future efforts focused on encouraging providers to discuss car seats during patient visits, increasing awareness of the American Academy of Pediatrics' rear-facing recommendation, and targeting high-risk populations may improve the prevalence of children who remain rear facing until 2 years of age.
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Acidentes de Trânsito/estatística & dados numéricos , Sistemas de Proteção para Crianças/estatística & dados numéricos , Equipamentos para Lactente/estatística & dados numéricos , Estudos Transversais , Desenho de Equipamento , Feminino , Humanos , Lactente , Masculino , Prevalência , Inquéritos e QuestionáriosRESUMO
Background Recent studies have suggested a correlation between susceptibility-diffusion mismatch and perfusion-diffusion mismatch in acute ischemic stroke patients. Purpose To determine the clinical and imaging associations of susceptibility-diffusion mismatch in patients with acute ischemic stroke in the middle cerebral artery (MCA) territory. Material and Methods Consecutive patients with MCA territory acute ischemic stroke, who had magnetic resonance imaging (MRI) performed with susceptibility-weighted imaging (SWI) and diffusion-weighted imaging (DWI) within 24 h of symptom onset or time last-seen-well, were included. Two neuroradiologists reviewed SWI scans for SWI-DWI mismatch defined by regionally increased vessel number or diameter on SWI extending beyond the DWI hyperintensity territory in the affected hemisphere. The stroke severity at admission was evaluated using the National Institutes of Health Stroke Scale (NIHSS) score. Poor clinical outcome was defined by a 3-month modified Rankin Scale (mRS) score >2. Results The SWI-DWI mismatch was identified in 44 (29.3%) of 150 patients included in this study. Patients with SWI-DWI mismatch had smaller admission infarct volumes (31.2 ± 44.7 versus 55.9 ± 117.7 mL, P = 0.045) and were younger (60.4 ± 18.9 versus 67.1 ± 15.5, P = 0.026). After correction for age, admission NIHSS score, and infarct volume, the SWI-DWI mismatch was associated with a 22.6% lower rate of poor clinical outcome using propensity score matching ( P = 0.032). In our cohort, thrombolytic therapy showed no significant effect on outcome. Conclusion The presence of SWI-DWI mismatch in acute MCA territory ischemic infarct is associated with smaller infarct volume. Moreover, SWI-DWI mismatch was associated with better outcome after correction for infarct size, severity of admission symptoms, and age.
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Isquemia Encefálica/diagnóstico , Imagem de Difusão por Ressonância Magnética , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Doença Aguda , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To estimate prevalence of car safety seat (CSS) misuse for newborns on hospital discharge; and to identify potential risk and protective factors for CSS misuse. STUDY DESIGN: We randomly sampled 291 mother-baby dyads from the newborn unit of an academic health center. Participants completed a survey and designated someone (themselves or another caregiver) to position their newborn in the CSS and install the CSS in their vehicle. Certified child passenger safety technicians assessed positioning and installation using nationally standardized criteria. To examine factors associated with CSS misuse, we used logistic regression to compute ORs and 95% CIs. RESULTS: A total of 291 families (81% of those eligible) participated. Nearly all (95%) CSSs were misused, with 1 or more errors in positioning (86%) and/or installation (77%). Serious CSS misuse occurred for 91% of all infants. Frequent misuses included harness and chest clip errors, incorrect recline angle, and seat belt/lower anchor use errors. Families with mothers of color (OR, 6.3; 95% CI, 1.8-21.6), non-English language (OR, 4.9; 95% CI, 1.1-21.2), Medicaid (OR, 10.3; 95% CI, 2.4-44.4), or lower educational level (OR, 4.5; 95% CI, 1.7-12.4) were more likely to misuse CSSs. However, families that worked with a child passenger safety technician before delivery were significantly less likely to misuse their CSSs (OR, 0.1; 95% CI, 0.0-0.4). CONCLUSION: Nearly all parents of newborn infants misused CSSs. Resources should be devoted to ensuring families with newborns leave the hospital correctly using their CSS.
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Sistemas de Proteção para Crianças , Equipamentos para Lactente , Segurança , Adulto , Etnicidade , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Recém-Nascido , Mães , Oregon , Alta do Paciente , Pediatria/normas , Risco , Inquéritos e Questionários , Meios de Transporte , Estados UnidosRESUMO
Firearms are involved in the injury and death of a large number of children each year from both intentional and unintentional causes. Gun ownership in homes with children is common, and pediatricians should incorporate evidence-based means to discuss firearms and protect children from gun-related injuries and violence. Safe storage of guns, including unloaded guns locked and stored separately from ammunition, can decrease risks to children, and effective tools are available that pediatricians can use in clinical settings to help decrease children's access to firearms. Furthermore, several community-based interventions led by pediatricians have effectively reduced firearm-related injury risks to children. Educational programs that focus on children's behavior around guns have not proven effective.
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Armas de Fogo , Ferimentos por Arma de Fogo/prevenção & controle , Criança , Mortalidade da Criança , Pré-Escolar , Feminino , Humanos , Masculino , Risco , Medição de Risco , Violência/prevenção & controle , Ferimentos por Arma de Fogo/epidemiologiaRESUMO
OBJECTIVE: To evaluate pediatricians' self-reported knowledge, attitudes, and dissemination practices regarding the new American Academy of Pediatrics' (AAP) child passenger safety (CPS) policy recommendations. STUDY DESIGN: A cross-sectional survey was distributed to pediatric primary care physicians via AAP e-mail distribution lists. Knowledge, attitudes, and practices related to current AAP CPS recommendations and the revised policy statement were ascertained. RESULTS: There were 718 respondents from 3497 physicians with active e-mail addresses, resulting in a 20.5% response rate, of which 533 were eligible based on the initial survey question. All 6 CPS knowledge and scenario-based items were answered correctly by 52.9% of the sample; these respondents were identified as the "high knowledge" group. Pediatricians with high knowledge were more likely to be female (P < .001), to have completed a pediatrics residency (vs medicine-pediatrics) (P = .03), and have a child between 4 and 7 years of age (P = .001). CPS information was distributed more frequently at routine health visits for patients 0-2 years of age vs those 4-12 years of age. Those with high knowledge were less likely to report several specific barriers to dissemination of CPS information, more likely to allot adequate time and discuss CPS with parents, and had greater confidence for topics related to all CPS topics. CONCLUSIONS: Although CPS knowledge is generally high among respondents, gaps in knowledge still exist. Knowledge is associated with attitudes, practices, barriers, and facilitators of CPS guideline dissemination. These results identify opportunities to increase knowledge and implement strategies to routinely disseminate CPS information in the primary care setting.
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Sistemas de Proteção para Crianças , Conhecimentos, Atitudes e Prática em Saúde , Médicos de Atenção Primária/estatística & dados numéricos , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Autorrelato , Estados UnidosRESUMO
OBJECTIVE: Unintentional injuries remain a leading cause of death for children and adolescents older than 1 year. Injury prevention has long been a cornerstone of anticipatory guidance. Previous studies have established the sustained efficacy of injury prevention anticipatory guidance in pediatric primary care. This study examines the topical emphasis of injury prevention anticipatory guidance by patient age, with special attention given to the rate of water safety anticipatory guidance across 4 patient age groups. METHODS: A nationwide, random sample of AAP member pediatricians was surveyed on their experiences, attitudes, and practices related to injury prevention anticipatory guidance, including barriers to delivering anticipatory guidance. RESULTS: Of the respondents who reported providing direct patient care, 92% considered injury prevention anticipatory guidance a priority issue. The content of that injury prevention guidance varied considerably by patient age. Roughly half (53%) reported counseling families with adolescents on water safety/drowning prevention, which represents a statistically significant decrease relative to other patient age groups. CONCLUSIONS: Reported injury prevention anticipatory guidance is high across different mechanisms of injury. However, fewer pediatricians deliver drowning prevention anticipatory guidance to adolescents than to younger patients. Targeted outreach and education to increase injury prevention anticipatory guidance, especially for adolescent patients, should be part of a multipronged approach to decrease drowning and other injury deaths.
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Afogamento , Adolescente , Criança , Humanos , Afogamento/prevenção & controle , Aconselhamento , Inquéritos e Questionários , Atitude , ÁguaRESUMO
Mechanosensory neurons that innervate the tongue provide essential information to guide feeding, speech, and social grooming. We use in vivo calcium imaging of mouse trigeminal ganglion neurons to identify functional groups of mechanosensory neurons innervating the anterior tongue. These sensory neurons respond to thermal and mechanical stimulation. Analysis of neuronal activity patterns reveal that most mechanosensory trigeminal neurons are tuned to detect moving stimuli across the tongue. Using an unbiased, multilayer hierarchical clustering approach to classify pressure-evoked activity based on temporal response dynamics, we identify five functional classes of mechanosensory neurons with distinct force-response relations and adaptation profiles. These populations are tuned to detect different features of touch. Molecular markers of functionally distinct clusters are identified by analyzing cluster representation in genetically marked neuronal subsets. Collectively, these studies provide a platform for defining the contributions of functionally distinct mechanosensory neurons to oral behaviors crucial for survival in mammals.
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Células Receptoras Sensoriais , Língua , Camundongos , Animais , Células Receptoras Sensoriais/fisiologia , Língua/inervação , Gânglio Trigeminal/fisiologia , Tato/fisiologia , MamíferosRESUMO
The carbazole CBL0137 (1) is a lead for drug development against human African trypanosomiasis (HAT), a disease caused by Trypanosoma brucei. To advance 1 as a candidate drug, we synthesized new analogs that were evaluated for the physicochemical properties, antitrypanosome potency, selectivity against human cells, metabolism in microsomes or hepatocytes, and efflux ratios. Structure-activity/property analyses of analogs revealed eight new compounds with higher or equivalent selectivity indices (5j, 5t, 5v, 5w, 5y, 8d, 13i, and 22e). Based on the overall compound profiles, compounds 5v and 5w were selected for assessment in a mouse model of HAT; while 5v demonstrated a lead-like profile for HAT drug development, 5w showed a lack of efficacy. Lessons from these studies will inform further optimization of carbazoles for HAT and other indications.
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Tripanossomicidas , Trypanosoma brucei brucei , Tripanossomíase Africana , Camundongos , Animais , Humanos , Tripanossomíase Africana/tratamento farmacológico , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêutico , Tripanossomicidas/química , Carbazóis/farmacologia , Carbazóis/uso terapêutico , Descoberta de DrogasRESUMO
Advocacy is at the heart of pediatrics and neonatal care. Historically and currently, numerous pediatricians have used their expertise to raise the voices of children and families to promote child health and welfare. Despite a lack of formal training in advocacy and health policy, many of the skills required for daily clinical care can, and ought to, be applied to affect systemic change within neonatology. Advocacy can no longer be considered an optional activity, but rather a core competency and professional responsibility. In this review, the authors describe the necessity and foundational principles for advocacy success as well as provide guidance, resources, and opportunities for neonatologists and clinicians providing newborn care.
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Neonatologia , Criança , Humanos , Recém-Nascido , Neonatologistas , PediatrasRESUMO
Firearms are the leading cause of death in children and youth 0 to 24 years of age in the United States. They are also an important cause of injury with long-term physical and mental health consequences. A multipronged approach with layers of protection focused on harm reduction, which has been successful in decreasing motor vehicle-related injuries, is essential to decrease firearm injuries and deaths in children and youth. Interventions should be focused on the individual, household, community, and policy level. Strategies for harm reduction for pediatric firearm injuries include providing anticipatory guidance regarding the increased risk of firearm injuries and deaths with firearms in the home as well as the principles of safer firearm storage. In addition, lethal means counseling for patients and families with individuals at risk for self-harm and suicide is important. Community-level interventions include hospital and community-based violence intervention programs. The implementation of safety regulations for firearms as well as enacting legislation are also essential for firearm injury prevention. Increased funding for data infrastructure and research is also crucial to better understand risks and protective factors for firearm violence, which can then inform effective prevention interventions. To reverse this trend of increasing firearm violence, it is imperative for the wider community of clinicians, public health advocates, community stakeholders, researchers, funders, and policy makers to collaboratively address the growing public health crisis of firearm injuries in US youth.
RESUMO
Firearms are the leading cause of death in children and youth 0 to 24 years of age in the United States. In 2020, firearms resulted in 10,197 deaths (fatality rate 9.91/100,000 youth 0-24 years old). Firearms are the leading mechanism of death in pediatric suicides and homicides. Increased access to firearms is associated with increased rates of firearm deaths. Substantial disparities in firearm injuries and deaths exist by age, gender, race, ethnicity, and sexual orientation and gender identity and for deaths related to legal intervention. Barriers to firearm access can decrease the risk to youth for firearm suicide, homicide, or unintentional shooting injury and death. Given the high lethality of firearms and the impulsivity associated with suicidal ideation, removing firearms from the home or securely storing them-referred to as lethal means restriction of firearms-is critical, especially for youth at risk for suicide. Primary care-, emergency department-, mental health-, hospital-, and community-based intervention programs can effectively screen and intervene for individuals at risk for harming themselves or others. The delivery of anticipatory guidance coupled with safety equipment provision improves firearm safer storage. Strong state-level firearm legislation is associated with decreased rates of firearm injuries and death. This includes legislation focused on comprehensive firearm licensing strategies and extreme risk protection order laws. A firm commitment to confront this public health crisis with a multipronged approach engaging all stakeholders, including individuals, families, clinicians, health systems, communities, public health advocates, firearm owners and nonowners, and policy makers, is essential to address the worsening firearm crisis facing US youth today.