RESUMO
One factor that contributes to the high prevalence of fetal alcohol spectrum disorder (FASD) is binge-like consumption of alcohol before pregnancy awareness. It is known that treatments are more effective with early recognition of FASD. Recent advances in retrospective motion correction for the reconstruction of three-dimensional (3D) fetal brain MRI have led to significant improvements in the quality and resolution of anatomical and diffusion MRI of the fetal brain. Here, a rhesus macaque model of FASD, involving oral self-administration of 1.5 g/kg ethanol per day beginning prior to pregnancy and extending through the first 60 d of a 168-d gestational term, was utilized to determine whether fetal MRI could detect alcohol-induced abnormalities in brain development. This approach revealed differences between ethanol-exposed and control fetuses at gestation day 135 (G135), but not G110 or G85. At G135, ethanol-exposed fetuses had reduced brainstem and cerebellum volume and water diffusion anisotropy in several white matter tracts, compared to controls. Ex vivo electrophysiological recordings performed on fetal brain tissue obtained immediately following MRI demonstrated that the structural abnormalities observed at G135 are of functional significance. Specifically, spontaneous excitatory postsynaptic current amplitudes measured from individual neurons in the primary somatosensory cortex and putamen strongly correlated with diffusion anisotropy in the white matter tracts that connect these structures. These findings demonstrate that exposure to ethanol early in gestation perturbs development of brain regions associated with motor control in a manner that is detectable with fetal MRI.
Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Encéfalo/fisiopatologia , Transtornos do Espectro Alcoólico Fetal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Imagem de Difusão por Ressonância Magnética , Modelos Animais de Doenças , Etanol/toxicidade , Feminino , Transtornos do Espectro Alcoólico Fetal/diagnóstico por imagem , Desenvolvimento Fetal/efeitos dos fármacos , Feto/diagnóstico por imagem , Feto/efeitos dos fármacos , Humanos , Macaca mulatta , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagem , Estudos RetrospectivosRESUMO
Certain life stressors having enduring physiological and behavioral consequences, in part by eliciting dramatic signaling shifts in monoamine neurotransmitters. High monoamine levels can overwhelm selective transporters like the serotonin transporter. This is when polyspecific transporters like plasma membrane monoamine transporter (PMAT, Slc29a4) are hypothesized to contribute most to monoaminergic signaling regulation. Here, we employed two distinct counterbalanced stressors-fear conditioning and swim stress-in mice to systematically determine how reductions in PMAT function affect heterotypic stressor responsivity. We hypothesized that male heterozygotes would exhibit augmented stressor responses relative to female heterozygotes. Decreased PMAT function enhanced context fear expression, an effect unexpectedly obscured by a sham stress condition. Impaired cued fear extinction retention and enhanced context fear expression in males were conversely unmasked by a sham swim condition. Abrogated corticosterone levels in male heterozygotes that underwent swim stress after context fear conditioning did not map onto any measured behaviors. In sum, male heterozygous mouse fear behaviors proved malleable in response to preceding stressor or sham stress exposure. Combined, these data indicate that reduced male PMAT function elicits a form of stress-responsive plasticity. Future studies should assess how PMAT is differentially affected across sexes and identify downstream consequences of the stress-shifted corticosterone dynamics.
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Medo , Animais , Feminino , Masculino , Camundongos , Corticosterona/análise , Extinção Psicológica , Proteínas de Membrana Transportadoras , Transdução de SinaisRESUMO
OBJECTIVE: To characterize the prevalence and presentation of laryngomalacia and efficacy of supraglottoplasty (SGP) in a cohort of patients with Pierre Robin Sequence (PRS). DESIGN: Retrospective cohort study. SETTING: Tertiary-care children's hospital. PATIENTS, PARTICIPANTS: Consecutive patients with PRS born between January 2010 and June 2018. MAIN OUTCOME MEASURES: Chart review included demographics, comorbid airway obstruction including laryngomalacia, timing of surgical interventions, clinical symptoms, sleep study data, and modified barium swallow study data.126 patients with PRS were included; 54% had an associated syndrome, 64% had an overt cleft palate, and 22% had a submucous cleft palate. 64/126 were noted to have laryngomalacia (51%). Patients with concurrent PRS and laryngomalacia were significantly more likely to have submucous cleft palate (P = .005) and present with aspiration with cough (P = .01) compared to patients with PRS without laryngomalacia. Patients with concurrent laryngomalacia and PRS showed a significant decrease in apnea-hypopnea index (AHI) and obstructive AHI (OAHI) after mandibular distraction, with a median AHI and OAHI improvement of 22.3 (P = .001) and 19.8 (P = .002), respectively. Patients who underwent only SGP did not show significant improvement in these parameters (P = .112 for AHI, P = .064 for OAHI).The prevalence of laryngomalacia in our PRS cohort was 51%. Patients with PRS and laryngomalacia are more likely to present with overt aspiration compared to patients with PRS without laryngomalacia. These data support that laryngomalacia does not appear to be a contraindication to pursuing MDO.
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Obstrução das Vias Respiratórias , Fissura Palatina , Laringomalácia , Osteogênese por Distração , Síndrome de Pierre Robin , Criança , Humanos , Lactente , Estudos Retrospectivos , Laringomalácia/epidemiologia , Laringomalácia/cirurgia , Laringomalácia/complicações , Síndrome de Pierre Robin/complicações , Síndrome de Pierre Robin/cirurgia , Prevalência , Fissura Palatina/complicações , Obstrução das Vias Respiratórias/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: Investigate associations between socioeconomic indicators of healthcare access with family compliance with cleft-related otologic and audiologic care within an interdisciplinary model. DESIGN: Retrospective case series. SUBJECTS AND SETTING: Children born 2005-2015 who presented to the Cleft-Craniofacial Clinic (CCC) at a quaternary care children's hospital. INTERVENTIONS: Associations between main outcome measures and Area Deprivation Index (ADI), median household income for zip code, distance from hospital, and insurance status were evaluated. MAIN OUTCOME MEASURES: Cleft types, ages at presentation to outpatient clinic (cleft, otolaryngology, and audiology), and ages at procedures (first tympanostomy tube insertion (TTI), lip repair, and palatoplasty) were measured. RESULTS: Most patients were male (147/230, 64%) with cleft lip and palate (157/230, 68%). Median age at first cleft, otolaryngology, and audiology visits were 7 days, 86 days, and 5.9 months, respectively. Private insurance predicted lower no-show rates (p = .04). Age at first CCC visit was younger for patients with private insurance (p = .04) and older for those who lived further from the hospital (p = .002). Age at lip repair was positively correlated with national ADI (p = .03). However, no socioeconomic status (SES) proxy or proximity to hospital was associated with delays in first otolaryngology or audiology examination or TTI. CONCLUSION: Once children become established within an interdisciplinary CCC, SES appears to bear little influence on cleft-related otologic and audiologic care. Future efforts should aim to elucidate which aspects of the interdisciplinary model maximize multisystem cleft care coordination and increase access for higher risk populations.
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Johnson, Bilovich, and Tuckett set out a helpful framework for thinking about how humans make decisions under radical uncertainty and contrast this with classical decision theory. We show that classical theories assume so little about psychology that they are not necessarily in conflict with this approach, broadening its appeal.
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Tomada de Decisões , Teoria da Decisão , Humanos , IncertezaRESUMO
Despite the robustness of DRD4 polymorphism associations with brain-based behavioral characteristics in candidate gene research, investigations have minimally explored associations between these polymorphisms and emotional responses. In particular, the prevalent single nucleotide polymorphism (SNP) -521C/T (rs1800955) in the promoter region of DRD4 remains unexplored relative to emotions. Here, two independent samples were evaluated using different emotion elicitation tasks involving social stimuli: Study 1 (N = 120) evoked positive and negative emotional responses to validated film clips; Study 2 (N = 122) utilized Cyberball to simulate social rejection and acceptance. Across studies, C/C individuals self-reported higher mean positive affect scores using Likert scales versus T carrier individuals, selectively when presented with neutral or negative (but not positive) social stimuli. The consistent findings across these two studies supports a functional consequence of this DRD4 SNP on emotion processing during changing social contexts. Continued investigation will help clarify if a C/C genotype enhances positive emotions under negative circumstances, or if the presence of the T allele reduces positive emotions, and how rs1800955 behavioral associations might generalize across different demographics. Future studies could also reveal if this SNP interacts with other changing environmental conditions to affect emotional responses, such as social limitations during the COVID-19 pandemic.
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Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D4 , Interação Social , Alelos , COVID-19 , Genótipo , Humanos , Pandemias , Receptores de Dopamina D4/genéticaRESUMO
Hazardous, heavy drinking increases risk for developing alcohol use disorder (AUD), which affects ~7% of adult Americans. Thus, understanding the molecular mechanisms promoting risk for heavy drinking is essential to developing more effective AUD pharmacotherapies than those currently approved by the FDA. Using genome-wide bisulfate sequencing, we identified DNA methylation (DNAm) signals within the nucleus accumbens core (NAcC) that differentiate nonheavy and heavy ethanol-drinking rhesus macaques. One differentially DNAm region (D-DMR) located within the gene neurobeachin (NBEA), which promotes synaptic membrane protein trafficking, was hypermethylated in heavy drinking macaques. A parallel study identified a similar NBEA D-DMR in human NAcC that distinguished alcoholic and nonalcoholic individuals. To investigate the role of NBEA in heavy ethanol drinking, we engineered a viral vector carrying a short hairpin RNA (shRNA) to reduce the expression of NBEA. Using two murine models of ethanol consumption: 4 days of drinking-in-the-dark and 4 weeks of chronic intermittent access, the knockdown of NBEA expression did not alter average ethanol consumption in either model. However, it did lead to a significant increase in the ethanol preference ratio. Following withdrawal, whole-cell patch clamp electrophysiological experiments revealed that Nbea knockdown led to an increase in spontaneous excitatory postsynaptic current amplitude with no alteration in spontaneous inhibitory postsynaptic currents, suggesting a specific role of NBEA in trafficking of glutamatergic receptors. Together, our findings suggest that NBEA could be targeted to modulate the preference for alcohol use.
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Consumo de Bebidas Alcoólicas/genética , Alcoolismo/genética , Proteínas de Transporte/genética , Proteínas do Tecido Nervoso/genética , Adulto , Idoso , Animais , Metilação de DNA/efeitos dos fármacos , Humanos , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Núcleo Accumbens/efeitos dos fármacosRESUMO
PURPOSE: Coronavirus Disease-2019 (COVID-19) mitigation measures have led to a sustained reduction in tympanostomy tube (TT) placement in the general population. The present aim was to determine if TT placement has also decreased in children at risk for chronic otitis media with effusion (COME), such as those with cleft palate (CP). MATERIALS AND METHODS: A cohort study with medical record review was performed including consecutive children, ages 0-17 years, undergoing primary palatoplasty at a tertiary children's hospital February 2019-January 2020 (pre-COVID) or May 2020-April 2021 (COVID). Revision palatoplasty (n = 29) was excluded. Patient characteristics and middle ear status pre-operatively and at palatoplasty were compared between groups using logistic regression or Wilcoxon rank-sum. RESULTS: The pre-COVID and COVID cohorts included 73 and 87 patients, respectively. Seventy (44%) were female and median age at palatoplasty was 13.5 months for CP ± cleft lip (CP ± L) and 5.5 years for submucous cleft palate (SMCP). In patients with CP ± L, TT were placed or in place and patent at palatoplasty in 28/38 (74%) pre-COVID and 37/50 (74%) during COVID (P = 0.97). In patients with SMCP, these proportions were 5/35 (14%) and 6/37 (16%), respectively (P = 0.82). Examining only patients <2 years of age also revealed no difference in TT placement pre-COVID versus COVID (P = 0.99). Finally, the prevalence and type of effusion during COVID was similar to pre-COVID. CONCLUSIONS: Reduced infectious exposure has not decreased TT placement or effusion at palatoplasty. Future work could focus on non-infectious immunologic factors underlying the maintenance of COME in these children.
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COVID-19/epidemiologia , Fissura Palatina/cirurgia , Ventilação da Orelha Média/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pandemias , SARS-CoV-2RESUMO
INTRODUCTION: Velopharyngeal insufficiency (VPI), a stigmatizing hallmark of palatal dysfunction, occurs in a wide spectrum of pediatric craniofacial conditions. The mainstays for surgical correction include palate repair and/or pharyngeal surgery. However, primary pharyngoplasty has a failure rate of 15% to 20%. Although revision pharyngoplasty may be necessary in those with persistent VPI, little is known regarding the indications for and outcomes after such procedures. The purpose of this study is to describe the authors' experience with indications for and outcomes after revision pharyngoplasty. METHODS: A single-center retrospective review was performed of all patients undergoing revision pharyngoplasty between 2002 and 2019. Demographic data and Pittsburgh Weighted Speech Scores, diagnoses, comorbidities, and complications were tabulated. Two-tailed Student t test was used, and a P value of 0.05 or less was considered statistically significant. RESULTS: Thirty-two patients (65.6% male) met inclusion criteria for this study. The most common diagnoses included cleft palate (68.8%), submucous cleft palate (SMCP, 18.8%), and congenital VPI (6.3%, likely occult SMCP). Most patients (84.4%) underwent palatoplasty before their initial pharyngoplasty. The primary indication for initial pharyngoplasty was VPI (mean age 7.1 ± 4.6 years). The most common indication for revision pharyngoplasty (mean age 11.2 ± 5.1 years) included persistent VPI (n = 22), followed by obstructive sleep apnea (OSA) (n = 11). Persistent VPI (n = 8) and OSA (n = 6) were the most common complications after secondary pharyngoplasty. Thirteen patients (40.6%) within the revision pharyngoplasty cohort required additional surgical intervention: 4 underwent tertiary pharyngoplasty, 4 underwent takedown for OSA (n = 3) or persistent VPI (n = 1), 3 underwent takedown and conversion Furlow for persistent VPI (n = 2), OSA (n = 2) and/or flap dehiscence (n = 1), and 2 underwent palatal lengthening with buccal myomucosal flaps for persistent VPI. Of the 4 patients who required a tertiary pharyngoplasty, the mean age at repair was 6.6 ± 1.1 years and their speech scores improved from 13.5 to 2.3 after tertiary pharyngoplasty (P = 0.11). The overall speech score after completion of all procedures improved significantly from 19 to 3.3. CONCLUSION: Patients who fail primary pharyngoplasty represent a challenging population. Of patients who underwent secondary pharyngoplasty, nearly half required a tertiary procedure to achieve acceptable speech scores or resolve complications.
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Fissura Palatina , Apneia Obstrutiva do Sono , Insuficiência Velofaríngea , Adolescente , Criança , Pré-Escolar , Fissura Palatina/cirurgia , Feminino , Humanos , Masculino , Faringe/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Insuficiência Velofaríngea/etiologia , Insuficiência Velofaríngea/cirurgiaRESUMO
Cardiac drugs with defined pharmacological parameters in horses are limited. The objective of this study was to characterize the pharmacokinetic properties and cardiovascular effects of intravenous and oral metoprolol tartrate (MET) in horses. In a 2-period randomized cross-over design, MET was administered IV (0.04 mg/kg) and PO (6 mg/kg) once to six healthy adult horses. Horses were monitored via continuous telemetry and non-invasive blood pressure (NIBP). Blood samples were serially collected for 72 h post-administration, and concentrations were determined by LC-MS/MS. Pharmacokinetics were modeled using a 3-compartment model and non-linear least squares regression. Median (range) MET concentration was 110 (40.1-197) ng/ml collected 1 min (0.0167 h) after a bolus IV administration. Maximum concentration (Cmax ) after PO administration was 2135 (1590-4170) ng/ml at 0.5 (0.25-0.5) hours. Oral bioavailability was 54% (17-100%). Median apparent volume of distribution was 0.39 (0.17-0.58) l/kg, clearance was 12.63 (11.41-18.94) ml/kg/min, and elimination half-life was 21.1 (7.46-34.36) minutes. No clinically relevant effects of IV or PO metoprolol were noted on cardiac rhythm or NIBP. Sweating was the most common side effect. The metoprolol doses used in this study achieve plasma concentrations reported to achieve ß-blockade in humans.
Assuntos
Metoprolol , Espectrometria de Massas em Tandem , Administração Oral , Animais , Área Sob a Curva , Cromatografia Líquida/veterinária , Estudos Cross-Over , Meia-Vida , Cavalos , Injeções Intravenosas/veterinária , Metoprolol/farmacocinética , Metoprolol/farmacologia , Espectrometria de Massas em Tandem/veterináriaRESUMO
PURPOSE: Persistent velopharyngeal insufficiency (VPI) following primary palatoplasty remains a difficult problem to treat. This study evaluates speech outcomes following revision palatoplasty with tissue augmentation using buccal myomucosal flaps (BMF) as an alternative to pharyngoplasty for patients with VPI. METHODS: A retrospective single-center review of revision palatoplasty with tissue augmentation at a tertiary pediatric hospital Cleft-Craniofacial Center between January 2017 and March 2021 was conducted. Patients with a history of previous palatoplasty, a diagnosis of persistent or recurrent VPI, and comprehensive pre- and postoperative speech evaluations who underwent revision palatoplasty with BMF were included. RESULTS: Twenty patients met inclusion criteria (35% female, 20% syndromic). Mean age at the time of revision palatoplasty with BMF was 9.7 years. Preoperatively, all patients had stigmatizing speech and received the recommendation for speech surgery; the mean Pittsburgh Weighted Speech Score (PWSS) was 14.3 ± 4.9. The mean postoperative PWSS at the most recent assessment was 4.2 ± 2.3, representing a statistically significant improvement from preoperative scores (P < .001). Mean follow-up time was 8.9 months. Following revision palatoplasty with BMF, only one patient has received the recommendation for further speech surgery. No complications were noted. CONCLUSION: In patients with VPI following primary palatoplasty, revision palatoplasty with tissue augmentation offers an alternative to pharyngoplasty. This approach preserves dynamic velopharyngeal function, improves speech outcomes, and should be considered an option when treating patients with post-primary palatoplasty VPI.
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Fissura Palatina , Insuficiência Velofaríngea , Humanos , Feminino , Criança , Masculino , Insuficiência Velofaríngea/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Fissura Palatina/cirurgia , Fissura Palatina/complicaçõesRESUMO
The oviduct/fallopian tube is a tube-like structure that extends from the uterus to the ovary. It is an essential reproductive organ that provides an environment for internal fertilization and preimplantation development. However, our knowledge of its regional and cellular heterogeneity is still limited. Here, we examined the anatomical complexity of mouse oviducts using modern imaging techniques and fluorescence reporter lines. We found that there are consistent coiling patterns and turning points in the coiled mouse oviduct that serve as reliable landmarks for luminal morphological regionalities. We also found previously unrecognized anatomical structures in the isthmus and uterotubal junction, which likely play roles in reproduction. Furthermore, we demarcated the ampulla-isthmus junction as a distinct region. Taken together, the oviduct mucosal epithelium has highly diverse structures with distinct epithelial cell populations, reflecting its complex functions in reproduction.
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Desenvolvimento Embrionário , Oviductos/anatomia & histologia , Reprodução , Animais , Feminino , Camundongos , Oviductos/citologiaRESUMO
BACKGROUND: Fetal alcohol spectrum disorder (FASD) is caused by prenatal alcohol exposure (PAE), the intake of ethanol (C2 H5 OH) during pregnancy. Features of FASD cover a range of structural and functional defects including congenital heart defects (CHDs). Folic acid and choline, contributors of methyl groups to one-carbon metabolism (OCM), prevent CHDs in humans. Using our avian model of FASD, we have previously reported that betaine, another methyl donor downstream of choline, prevents CHDs. The CHD preventions are substantial but incomplete. Ethanol causes oxidative stress as well as depleting methyl groups for OCM to support DNA methylation and other epigenetic alterations. To identify more compounds that can safely and effectively prevent CHDs and other effects of PAE, we tested glutathione (GSH), a compound that regulates OCM and is known as a "master antioxidant." METHODS/RESULTS: Quail embryos injected with a single dose of ethanol at gastrulation exhibited congenital defects including CHDs similar to those identified in FASD individuals. GSH injected simultaneously with ethanol not only prevented CHDs, but also improved survival and prevented other PAE-induced defects. Assays of hearts at 8 days (HH stage 34) of quail development, when the heart normally has developed 4-chambers, showed that this single dose of PAE reduced global DNA methylation. GSH supplementation concurrent with PAE normalized global DNA methylation levels. The same assays performed on quail hearts at 3 days (HH stage 19-20) of development, showed no difference in global DNA methylation between controls, ethanol-treated, GSH alone, and GSH plus ethanol-treated cohorts. CONCLUSIONS: GSH supplementation shows promise to inhibit effects of PAE by improving survival, reducing the incidence of morphological defects including CHDs, and preventing global hypomethylation of DNA in heart tissues.
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Metilação de DNA/efeitos dos fármacos , Transtornos do Espectro Alcoólico Fetal/prevenção & controle , Glutationa/uso terapêutico , Cardiopatias Congênitas/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal , Consumo de Bebidas Alcoólicas/efeitos adversos , Animais , Depressores do Sistema Nervoso Central/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Etanol/efeitos adversos , Feminino , Glutationa/farmacologia , Cardiopatias Congênitas/induzido quimicamente , Gravidez , CodornizRESUMO
Two theories address the origin of repeating patterns, such as hair follicles, limb digits, and intestinal villi, during development. The Turing reaction-diffusion system posits that interacting diffusible signals produced by static cells first define a prepattern that then induces cell rearrangements to produce an anatomical structure. The second theory, that of mesenchymal self-organisation, proposes that mobile cells can form periodic patterns of cell aggregates directly, without reference to any prepattern. Early hair follicle development is characterised by the rapid appearance of periodic arrangements of altered gene expression in the epidermis and prominent clustering of the adjacent dermal mesenchymal cells. We assess the contributions and interplay between reaction-diffusion and mesenchymal self-organisation processes in hair follicle patterning, identifying a network of fibroblast growth factor (FGF), wingless-related integration site (WNT), and bone morphogenetic protein (BMP) signalling interactions capable of spontaneously producing a periodic pattern. Using time-lapse imaging, we find that mesenchymal cell condensation at hair follicles is locally directed by an epidermal prepattern. However, imposing this prepattern's condition of high FGF and low BMP activity across the entire skin reveals a latent dermal capacity to undergo spatially patterned self-organisation in the absence of epithelial direction. This mesenchymal self-organisation relies on restricted transforming growth factor (TGF) ß signalling, which serves to drive chemotactic mesenchymal patterning when reaction-diffusion patterning is suppressed, but, in normal conditions, facilitates cell movement to locally prepatterned sources of FGF. This work illustrates a hierarchy of periodic patterning modes operating in organogenesis.
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Folículo Piloso/embriologia , Fator de Crescimento Transformador beta/fisiologia , Animais , Padronização Corporal , Diferenciação Celular , Feminino , Perfilação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos , Transdução de Sinais , Pele/citologia , Pele/embriologia , Pele/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
OBJECTIVE: To determine whether orthodontic/dentofacial orthopedic maxillary protraction face mask therapy induces changes in velopharyngeal functioning in a cohort of pediatric patients having cleft palate with or without cleft lip. DESIGN: Retrospective chart review. SETTING: A children's hospital in the United States. PARTICIPANTS: Forty-three pediatric patients with cleft palate, with or without cleft lip, syndromic or with isolated clefts, who received face mask therapy from January 2009 to April 2016. INTERVENTION: Clinical data were extracted for review and analysis from medical records obtained from the Cleft Database/Research Registry (CDB-RR). MAIN OUTCOME MEASURES: Pittsburgh Weighted Speech Scores (PWSS) before and after therapy. RESULTS: There was a significant increase in PWSS after face mask therapy for patients with a PWSS score of 0 prior to treatment. Patients with PWSS >0 before treatment remained largely stable after face mask therapy. Maxillary advancement was not significantly associated with change in PWSS or fistula presence/absence. CONCLUSIONS: There is an increased risk of velopharyngeal insufficiency with maxillary protraction face mask treatment in patients with cleft palate. Patient counseling and obtaining consent regarding speech changes during treatment are recommended.
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Fenda Labial , Fissura Palatina , Insuficiência Velofaríngea , Criança , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To determine whether timing of palatoplasty (early, standard, or late) is associated with speech and language outcomes in children with cleft palate. DESIGN: Retrospective case series. SETTING: Tertiary care children's hospital. PARTICIPANTS: Records from 733 children born between 2005 and 2015 and treated at the Cleft Craniofacial Clinic of a tertiary children's hospital were retrospectively reviewed. Exclusion criteria were cleft repair at an outside hospital, intact secondary palate, absence of postpalatoplasty speech evaluation, syndromes, staged palatoplasty, and introduction to clinic after 12 months of age. Data from 232 children with cleft palate ± cleft lip were analyzed. INTERVENTIONS: Palatoplasty. MAIN OUTCOME MEASURES: Speech/language delays and disorders at 20 months and 5 years of age based on formal hospital or community-based testing or screening evaluation in the Cleft Craniofacial Clinic; additional speech surgery. RESULTS: Median age at palatoplasty was 12.6 months (range: 8.8-21.9 months). Age at palatoplasty was classified as early (<11 months, n = 28), standard (11-13 months, n = 158), or late (>13 months, n = 46). Late palatoplasty was associated with increased odds of speech/language delays and speech therapy at 20 months, and language delays at 5 years, compared with standard or early palatoplasty (P < .05 for all comparisons). However, speech sound production disorders, velopharyngeal incompetence, tube replacement, and hearing loss were not significantly associated with age at palatoplasty. CONCLUSIONS: Late palatoplasty may be associated with short- and long-term delays in speech/language development. Future studies with standardized surgical technique/timing and outcome measures are required to more definitively describe the impact of age at palatoplasty on speech/language development.
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Fissura Palatina , Insuficiência Velofaríngea , Criança , Humanos , Lactente , Estudos Retrospectivos , Fala , Resultado do TratamentoRESUMO
Cell proliferation is typically incorporated into stochastic mathematical models of cell migration by assuming that cell divisions occur after an exponentially distributed waiting time. Experimental observations, however, show that this assumption is often far from the real cell cycle time distribution (CCTD). Recent studies have suggested an alternative approach to modelling cell proliferation based on a multi-stage representation of the CCTD. In this paper we investigate the connection between the CCTD and the speed of the collective invasion. We first state a result for a general CCTD, which allows the computation of the invasion speed using the Laplace transform of the CCTD. We use this to deduce the range of speeds for the general case. We then focus on the more realistic case of multi-stage models, using both a stochastic agent-based model and a set of reaction-diffusion equations for the cells' average density. By studying the corresponding travelling wave solutions, we obtain an analytical expression for the speed of invasion for a general N-stage model with identical transition rates, in which case the resulting cell cycle times are Erlang distributed. We show that, for a general N-stage model, the Erlang distribution and the exponential distribution lead to the minimum and maximum invasion speed, respectively. This result allows us to determine the range of possible invasion speeds in terms of the average proliferation time for any multi-stage model.
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Ciclo Celular/fisiologia , Movimento Celular/fisiologia , Modelos Biológicos , Fatores de TempoRESUMO
Equations (9) and (10) were transcribed incorrectly.
RESUMO
Based on existing laboratory research on the visual physiology of walleye Sander vitreus, we tested colours of known spectral sensitivity (i.e., green and orange) using constant and strobing (5 Hz) illumination with an LED-based light guidance device (LGD). Hatchery-reared age 0 and 2 years S. vitreus were exposed to these four light combinations as well as an unilluminated control treatment during day and night trials. Age 2 years S. vitreus generally avoided the LGD when light was produced (negative phototaxis) compared with the control, with continuous illumination having a greater effect than strobing. The proportions of both age 0 and 2 year fish exiting illuminating zones of the trial arena did not differ with light colour or strobe rate, suggesting that phototactic behaviours in S. vitreus do not change with ontogeny in these age classes. Our findings confirm that typical behavioural responses of S. vitreus to light stimuli are characterised by avoidance and provide evidence that the use of light for behavioural guidance (deterrence) may be effective at reducing entrainment and impingement of this species on hydraulic barriers during migrations, independent of ontogenetic stage.
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Comportamento Animal/efeitos da radiação , Luz , Perciformes/fisiologia , Fototaxia , Migração Animal , Animais , Conservação dos Recursos Naturais/métodosRESUMO
OBJECTIVE: To describe the impact of timing of tympanostomy tube insertion on the number of tubes received and complications in children with routine tube placement. DESIGN: Retrospective case series. SETTING: Tertiary care children's hospital. PARTICIPANTS: Records from a consecutive sample of 401 children with cleft palate were reviewed. Sixty-five patients with isolated cleft palate and 82 patients with cleft lip and palate had follow-up until 5 years of age and were included. INTERVENTIONS: Tympanostomy tubes. MAIN OUTCOME MEASURE(S): Number of tubes received and tube-related complications. The hypothesis was formulated prior to data collection. RESULTS: Males comprised 55.8% of included patients, and tubes were placed in 98.6% of patients at a median age of 6.5 months. Effusion was documented at first tube placement for 96.5% of patients. Most (67.4%) patients required replacement of tubes, and 10.6% required long-term tubes. Complications included otorrhea (71.0%), myringosclerosis (35.2%), granulation (22.8%), perforation (17.9%), retained tubes (5.5%), and cholesteatoma (1.4%). Cleft lip and palate (P < .001) and otorrhea (P = .023) were associated with tube placement before palatoplasty. Patients with tube placement before palatoplasty (P = .033), genetic disorders (P = .007), failed newborn hearing screen (P = .012), otorrhea (P < .001), and granulation (P < .001) received more tubes. CONCLUSIONS: Nearly universal effusion in patients with cleft palate supports the need for routine tube placement. The potential for otorrhea and requiring more tubes should be weighed against the risks associated with prolonged effusion when considering tube placement before palatoplasty.